Granted Patent
B2
US 12,258,580 · App. 16/760,240 · Granted Mar 25, 2025
Process for generating therapeutic compositions of engineered cells
Inventors:
Sarah Y. Lee (Mercer Island, WA); Pascal Beauchesne (Seattle, WA); Mark L. Bonyhadi (Sammamish, WA); Ryan L. Crisman (Seattle, WA); Ryan P. Larson (Seattle, WA); Mary Mallaney (Seattle, WA); Christopher Glen Ramsborg (Seattle, WA); Clinton Weber (Seattle, WA); John Matthew Wesner (Seattle, WA); Nathan Yee (Seattle, CA)
Assignee:
Juno Therapeutics, Inc.
C12N5/0636A61K39/4611A61K39/4631A61K39/464412A61K2239/48C12N2501/2302C12N2501/2307C12N2501/2315C12N2501/999C12N2510/00
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Abstract
The present disclosure provides methods for genetically engineering T cells, such as CD4+ T cells, for use in cell therapy. In some aspects, the provided methods include one or more steps for incubating the cells under stimulating conditions, introducing a recombinant polypeptide to the cells through transduction or transfection, and cultivating the cells under conditions that promote proliferation and/or expansion. In some aspects, the incubation and/or the cultivation is performed in the presence of recombinant IL-2. In some aspects, the provided methods are an efficient, reliable means to produce genetically engineered T cells with a high degree of success.
Claims (58)
1. A method for producing a composition of engineered cells, the method comprising:
(a) incubating an input composition comprising T cells enriched for one or both of CD4+ and CD8+ primary human T cells, thereby generating a stimulated composition, wherein:
the primary human T cells are from a human subject having a disease or condition; and
the incubating is carried out under one or more stimulating conditions, the stimulating conditions comprising the presence of (i) an anti-CD3 antibody or antibody fragment thereof and an anti-CD28 antibody or antibody fragment thereof, and (ii) recombinant IL-2 and recombinant IL-15, wherein the concentration of recombinant IL-2 is from about 10 IU/mL to about 200 IU/mL and the concentration of recombinant IL-15 is from about 1 IU/mL to about 25 IU/mL;
(b) introducing a recombinant receptor into cells of the stimulated composition, thereby generating an engineered composition comprising engineered T cells, wherein the recombinant receptor is capable of binding to a target antigen that is expressed on a cell of the disease or condition; and
(c) cultivating the engineered composition under conditions to promote expansion of the engineered T cells, thereby producing an output composition comprising the engineered T cells that is suitable for an autologous cell therapy to treat the disease or condition of the subject, wherein:
(i) the cultivating is carried out in the presence of:
(1) recombinant IL-2 and recombinant IL-15, wherein the concentration of recombinant IL-2 is from about 50 IU/mL to about 500 IU/mL and the concentration of recombinant IL-15 is from about 5 IU/mL to about 50 IU/mL; and
(2) a surfactant, wherein the surfactant is a poloxamer added during the cultivating step;
(ii) at least a portion of the cultivating is performed with perfusion; and
(iii) the cultivating is performed for 2 days to 8 days, inclusive, wherein the cultivating is performed at least until the output composition comprises 4-fold or greater viable T cells compared to the composition prior to the cultivating; and
(d) collecting cells of the output composition after at most 8 days of the cultivating.
2. The method of claim 1 , wherein the incubating is further carried out in the presence of recombinant IL-7.
3. The method of claim 2 , wherein:
the concentration of recombinant IL-7 is from about 100 IU/mL to about 1000 IU/mL.
4. The method of claim 1 , wherein the input composition comprises about 200×10 6 cells to about 300×10 6 cells.
5. The method of claim 1 , wherein the input composition comprises greater than about 70% primary human T cells.
6. The method of claim 1 , wherein the input composition comprises greater than about 90% primary human T cells.
7. The method of claim 1 , wherein the incubating is carried out in the presence of one or more antioxidants.
8. The method of claim 7 , wherein the one or more antioxidants comprise a glutathione precursor.
9. The method of claim 7 , wherein the one or more antioxidants comprise N-acetylcysteine (NAC), 2,3-dimercaptopropanol (DMP), L-2-oxo-4-thiazolidinecarboxylate (OTC), lipoic acid, S-allyl cysteine, or methylmethionine sulfonium chloride.
10. The method of claim 7 , wherein the one or more antioxidants comprise N-acetyl cysteine (NAC).
11. The method of claim 10 , wherein the concentration of NAC is from 0.2 mg/mL to 2.0 mg/mL.
12. The method of claim 1 , wherein the anti-CD3 antibody or antibody fragment thereof and the anti-CD28 antibody or antibody fragment thereof are present on the surface of a bead.
13. The method of claim 12 , wherein the ratio of beads to cells is from 2:1 to 0.5:1 or from about 2:1 to about 0.5:1.
14. The method of claim 1 , wherein the introducing comprises transducing cells of the stimulated composition with a viral vector comprising a polynucleotide encoding the recombinant receptor.
15. The method of claim 14 , wherein the viral vector is a retroviral vector.
16. The method of claim 1 , wherein the recombinant receptor is a T-cell receptor (TCR) or antigen-binding fragment thereof.
17. The method of claim 1 , wherein the recombinant receptor is a chimeric antigen receptor (CAR).
18. The method of claim 1 , wherein the recombinant receptor is an anti-CD19 CAR.
19. The method of claim 1 , wherein the introducing is carried out in the presence of a transduction adjuvant.
20. The method of claim 19 , wherein the transduction adjuvant is protamine sulfate.
21. The method of claim 20 , wherein the concentration of protamine sulfate is from 1 μg/mL to 50 μg/mL.
22. The method of claim 1 , wherein the cultivating is further carried out in the presence of recombinant IL-7.
23. The method of claim 22 , wherein:
the concentration of recombinant IL-7 during the cultivating is from about 500 IU/mL to about 2000 IU/mL.
24. The method of claim 1 , wherein the concentration of the poloxamer is from 0.5 μL/mL to 5 μL/mL.
25. The method of claim 1 , wherein the anti-CD3 antibody or antibody fragment thereof and the anti-CD28 antibody or antibody fragment thereof are removed from the engineered composition prior to the cultivating.
26. The method of claim 25 , wherein the anti-CD3 antibody or antibody fragment thereof and the anti-CD28 antibody or antibody fragment thereof are removed from 3 days to 6 days after the initiation of the incubating.
27. The method of claim 1 , wherein the output composition comprises at least 1200×10 6 viable T cells.
28. The method of claim 1 , wherein the amount of time between the initiation of the incubating and the collecting is from 9 days to 13 days or from about 9 days to about 13 days.
29. The method of claim 1 , wherein the method is performed in less than 21 days, inclusive.
30. The method of claim 1 , further comprising formulating cells of the output composition for cryopreservation or administration to the human subject.
31. The method of claim 1 , wherein for a plurality of input compositions from different biological samples from a plurality of different human subjects having the disease or condition, output compositions are each produced in less than 21 days after the incubating of the plurality of input compositions for greater than 85% of the plurality of input compositions.
32. The method of claim 1 , wherein the disease or condition is a cancer.
33. The method of claim 1 , wherein during at least a portion of the cultivating, the cells are monitored for cell viability, concentration, density, number, or a combination of any of the foregoing.
34. The method of claim 33 , wherein the monitoring is carried out by differential digital holography microscopy (DDHM).
35. The method of claim 1 , wherein the input composition is a first input composition enriched in CD8+ primary human T cells, and the method further comprises:
(a) separately incubating, under stimulating conditions, a second input composition comprising T cells enriched for CD4+ primary human T cells, wherein:
the T cells enriched for CD4+ primary human T cells are isolated from the same biological sample from the human subject as the T cells enriched for CD8+ primary human T cells; and
the stimulating conditions comprise the presence of (i) a stimulatory reagent capable of activating one or more intracellular signaling domains of one or more components of a TCR complex and/or one or more intracellular signaling domains of one or more costimulatory molecules and (ii) one or more cytokines, thereby generating a second stimulated composition; and
(b) introducing a recombinant receptor into the second stimulated composition, thereby generating a second engineered composition comprising engineered T cells.
36. The method of claim 35 , wherein the recombinant receptor that is introduced into the second stimulated composition is the same recombinant receptor that is introduced into the first stimulated composition.
37. The method of claim 35 , wherein the one or more cytokines present during the stimulating of the second input composition comprise recombinant IL-2, recombinant IL-7, and recombinant IL-15.
38. The method of claim 1 , wherein the cultivating is initiated under conditions with no perfusion, and the perfusion is initiated when the concentration of the cells increases to reach a predetermined concentration.
39. The method of claim 38 , wherein the predetermined concentration is, is about, or is at least 0.1 ×10 6 cells/mL.
40. The method of claim 38 , wherein the perfusion rate is increased when the concentration of the cells increases to reach a second predetermined cell concentration.
41. The method of claim 40 , wherein the second predetermined concentration is, is about, or is at least 0.6 ×10 6 cells/mL.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 29, 2020
From: WESNER, JOHN MATTHEW; WEBER, CLINTON; RAMSBORG, CHRISTOPHER GLEN; MALLANEY, MARY; LEE, SARAH Y.; LARSON, RYAN P.; CRISMAN, RYAN L.; BONYHADI, MARK L.; BEAUCHESNE, PASCAL; YEE, NATHAN
To: JUNO THERAPEUTICS, INC.
Reel/Frame 053344/0474 →
Continuity (4)
Provisional Application
62721603
· Aug 22, 2018
Provisional Application
62596771
· Dec 8, 2017
Provisional Application
62580409
· Nov 1, 2017
References Cited (400)
US 4452773A
· Molday
· 1984
[cited by applicant]
US 4690915A
· Rosenberg
· 1987
[cited by applicant]
US 4795698A
· Owen
· 1989
[cited by applicant]
US 5087616A
· Myers
· 1992
[cited by applicant]
US 5168062A
· Stinski
· 1992
[cited by applicant]
US 5200084A
· Liberti
· 1993
[cited by applicant]
US 5219740A
· Miller
· 1993
[cited by applicant]
US 5385839A
· Stinski
· 1995
[cited by applicant]
US 5773224A
· Grandics et al.
· 1998
[cited by applicant]
US 5994136A
· Naldini et al.
· 1999
[cited by applicant]
US 6013516A
· Verma et al.
· 2000
[cited by applicant]
US 6040177A
· Riddell et al.
· 2000
[cited by applicant]
US 6123655A
· Fell
· 2000
[cited by applicant]
US 6207453B1
· Maass
· 2001
[cited by applicant]
US 6410319B1
· Raubitschek
· 2002
[cited by applicant]
US 6451995B1
· Cheung
· 2002
[cited by applicant]
US 6733433B1
· Fell
· 2004
[cited by applicant]
US 7070995B2
· Jensen
· 2006
[cited by applicant]
US 7265209B2
· Jensen
· 2007
[cited by applicant]
US 7354762B2
· Jensen
· 2008
[cited by applicant]
US 7362449B2
· Dubois et al.
· 2008
[cited by applicant]
US 7446179B2
· Jensen
· 2008
[cited by applicant]
US 7446190B2
· Sadelain
· 2008
[cited by applicant]
US 7446191B2
· Jensen
· 2008
[cited by applicant]
US 8008450B2
· Williams et al.
· 2011
[cited by applicant]
US 8153765B2
· Park et al.
· 2012
[cited by applicant]
US 8324353B2
· Jensen
· 2012
[cited by applicant]
US 8339645B2
· Nakawaki
· 2012
[cited by applicant]
US 8389282B2
· Sadelain et al.
· 2013
[cited by applicant]
US 8479118B2
· Lyndersay et al.
· 2013
[cited by applicant]
US 8603477B2
· Afar et al.
· 2013
[cited by applicant]
US 8802374B2
· Jensen
· 2014
[cited by applicant]
US 8822647B2
· Jensen
· 2014
[cited by applicant]
US 8911993B2
· June et al.
· 2014
[cited by applicant]
US 9684281B2
· Mathuis et al.
· 2017
[cited by applicant]
US 9904248B2
· Mathuis et al.
· 2018
[cited by applicant]
US 20020131960A1
· Sadelain
· 2002
[cited by applicant]
US 20080085532A1
· Gorlach et al.
· 2008
[cited by applicant]
US 20080171951A1
· Fell
· 2008
[cited by applicant]
US 20110070581A1
· Gupta
· 2011
[cited by applicant]
US 20110293667A1
· Baksh et al.
· 2011
[cited by applicant]
US 20120189622A1
· Tesar et al.
· 2012
[cited by applicant]
US 20130149337A1
· Cooper et al.
· 2013
[cited by applicant]
US 20150202286A1
· June et al.
· 2015
[cited by applicant]
US 20170209492A1
· June et al.
· 2017
[cited by applicant]
US 20200016199A1
· Turtle et al.
· 2020
[cited by applicant]
US 20200239910A1
· Bonyhadi
· 2020
[cited by applicant]
US 20210017249A1
· Sather et al.
· 2021
[cited by applicant]
US 20220008465A1
· Trede et al.
· 2022
[cited by applicant]
US 20220031746A1
· Gillenwater et al.
· 2022
[cited by applicant]
US 20220088070A1
· Albertson et al.
· 2022
[cited by applicant]
US 20230071910A1
· Farazi
· 2023
[cited by applicant]
US 20230090117A1
· Haig et al.
· 2023
[cited by applicant]
US 20230090176A1
· Ramsborg et al.
· 2023
[cited by applicant]
US 20240115612A1
· Albertson et al.
· 2024
[cited by applicant]
CN 103305464
· 2013
[cited by applicant]
CN 103503438
· 2014
[cited by applicant]
CN 104450614A
· 2015
[cited by applicant]
CN 106635955A
· 2017
[cited by applicant]
CN 106754670A
· 2017
[cited by applicant]
CN 106801032
· 2017
[cited by applicant]
CN 106834218
· 2017
[cited by applicant]
EP 0452342
· 1991
[cited by applicant]
EP 1631788
· 2006
[cited by applicant]
EP 2537416
· 2012
[cited by applicant]
EP 3372670
· 2018
[cited by applicant]
JP 2006525013
· 2006
[cited by applicant]
WO WO1996013593
· 1996
[cited by applicant]
WO WO1996018105
· 1996
[cited by applicant]
WO WO1998040510
· 1998
[cited by applicant]
WO WO1999018129
· 1999
[cited by applicant]
WO WO1999025817
· 1999
[cited by applicant]
WO WO1999060120
· 1999
[cited by applicant]
WO WO2000014257
· 2000
[cited by applicant]
WO WO2000038762
· 2000
[cited by applicant]
WO WO2000043551
· 2000
[cited by applicant]
WO WO2003020763
· 2003
[cited by applicant]
WO WO2004029221
· 2004
[cited by applicant]
WO WO2004033685
· 2004
[cited by applicant]
WO WO2004096975
· 2004
[cited by applicant]
WO WO2006000830
· 2006
[cited by applicant]
WO WO2006099875
· 2006
[cited by applicant]
WO WO2007117602
· 2007
[cited by applicant]
WO WO2008035631
· 2008
[cited by applicant]
WO WO2009003493
· 2009
[cited by applicant]
WO WO2009072003
· 2009
[cited by applicant]
WO WO2009072006
· 2009
[cited by applicant]
WO WO2009076524
· 2009
[cited by applicant]
WO WO2009090929
· 2009
[cited by applicant]
WO WO2011044186
· 2011
[cited by applicant]
WO WO2012062904
· 2012
[cited by applicant]
WO WO2012081650
· 2012
[cited by applicant]
WO WO2012092612
· 2012
[cited by applicant]
WO WO2012129514
· 2012
[cited by applicant]
WO WO2013011011
· 2013
[cited by applicant]
WO WO2013038272
· 2013
[cited by applicant]
WO WO2013062365
· 2013
[cited by applicant]
WO WO2013071154
· 2013
[cited by applicant]
WO WO2013123061
· 2013
[cited by applicant]
WO WO2013124474
· 2013
[cited by applicant]
WO WO2013126726
· 2013
[cited by applicant]
WO WO2013166321
· 2013
[cited by applicant]
WO WO2014011984
· 2014
[cited by applicant]
WO WO2014011996
· 2014
[cited by applicant]
WO WO2014031687
· 2014
[cited by applicant]
WO WO2014055668
· 2014
[cited by applicant]
WO WO2014210064
· 2014
[cited by applicant]
WO WO2015095895
· 2015
[cited by applicant]
WO WO2015157252
· 2015
[cited by applicant]
WO WO2015157384
· 2015
[cited by applicant]
WO WO2015158868
· 2015
[cited by applicant]
WO WO2015164675
· 2015
[cited by applicant]
WO WO2015164745
· 2015
[cited by applicant]
WO WO2015181253
· 2015
[cited by applicant]
WO WO2016019300
· 2016
[cited by applicant]
WO WO2016028896
· 2016
[cited by applicant]
WO WO2016033570
· 2016
[cited by applicant]
WO WO2016073602
· 2016
[cited by applicant]
WO WO2016090190
· 2016
[cited by applicant]
WO WO2016090312
· 2016
[cited by applicant]
WO WO2016090320
· 2016
[cited by applicant]
WO WO2016090327
· 2016
[cited by applicant]
WO WO2016090329
· 2016
[cited by applicant]
WO WO2016090369
· 2016
[cited by applicant]
WO WO2016090369A1
· 2016
[cited by examiner]
WO WO2016164580
· 2016
[cited by applicant]
WO WO2016164731
· 2016
[cited by applicant]
WO WO2016172606
· 2016
[cited by applicant]
WO WO2016191755
· 2016
[cited by applicant]
WO WO2016191756
· 2016
[cited by applicant]
WO WO2017035362
· 2016
[cited by applicant]
WO WO2017015427
· 2017
[cited by applicant]
WO WO2017015490
· 2017
[cited by applicant]
WO WO2017019848
· 2017
[cited by applicant]
WO WO2017023803
· 2017
[cited by applicant]
WO WO2017027291
· 2017
[cited by applicant]
WO WO2017049166
· 2017
[cited by applicant]
WO WO2017053889
· 2017
[cited by applicant]
WO WO2017058850
· 2017
[cited by applicant]
WO WO2017068421
· 2017
[cited by applicant]
WO WO2017096329
· 2017
[cited by applicant]
WO WO2017156479
· 2017
[cited by applicant]
WO WO2017157505
· 2017
[cited by applicant]
WO WO2017161353
· 2017
[cited by applicant]
WO WO2017156479A1
· 2017
[cited by examiner]
WO WO2017177137
· 2017
[cited by applicant]
WO WO2017214207
· 2017
[cited by applicant]
WO WO2018106732
· 2018
[cited by applicant]
WO WO2018157171
· 2018
[cited by applicant]
WO WO2018162352
· 2018
[cited by applicant]
WO WO2018191723
· 2018
[cited by applicant]
WO WO2018223101
· 2018
[cited by applicant]
WO WO2019109053
· 2019
[cited by applicant]
WO WO2019113556
· 2019
[cited by applicant]
WO WO2019113557
· 2019
[cited by applicant]
WO WO2019213184
· 2019
[cited by applicant]
WO WO2020033927
· 2020
[cited by applicant]
WO WO2020102770
· 2020
[cited by applicant]
WO WO2020113188
· 2020
[cited by applicant]
WO WO2020113194
· 2020
[cited by applicant]
WO WO2021151008
· 2021
[cited by applicant]
Finney et. al., (J Immunol, 172(1): 104-113, (2004) (Year: 2004).
[cited by examiner]
Levine et. al. 4:92-101, (2017) (Year: 2017).
[cited by examiner]
Chang et. al., 156:358-365, (2017) (Year: 2017).
[cited by examiner]
Kemper et. al., J Biomedical Optics, 15(3), 036009, (2010) (Year: 2010).
[cited by examiner]
Marthandan et. al. Immunity & Ageing, 10(7): 1-16, (2013) (Year: 2013).
[cited by examiner]
Bondanza (Blood, 117(24):6469-6478, (2011) (Year: 2011).
[cited by examiner]
Al-Shanti and Aldahoudi (Immunological Investigations, 36:85-104, (2007)) (Year: 2007).
[cited by examiner]
Akronbiotech 1-9 (2023) (Year: 2023).
[cited by examiner]
Marenghi et. al. GE 1-2 (2014) (Year: 2014).
[cited by examiner]
U.S. Appl. No. 16/769,971, filed Jun. 4, 2020, by Majacic et al.
[cited by applicant]
U.S. Appl. No. 16/770,052, filed Jun. 4, 2020, by Pascal et al.
[cited by applicant]
Abramson et al., “Updated safety and long term clinical outcomes in Transcend NHL 001, pivotal trial of lisocabtagene maraleucel (JCAR017) in R/R aggressive NHL,” J Clin Oncol (2018) 36(15_suppl):7505-7505.
[cited by applicant]
Abramson et al., “High durable CR rates in Relapsed/Refractory (R/R) Aggressive B-NHL Treated with the CD19-Directed CAR T Cell Product JCAR017 (Transcend NHL 001): Defined Composition Allows for Dose-Finding and Defini…
[cited by applicant]
Abramson et al., “Transcend NHL 001: Ininunotherapy with the CD19-Directed CAR T-Cell Product JCARO17 Results in High Complete Response Rates in Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma,” Blood (2016) 128(22):…
[cited by applicant]
Aksoy et al., “Human primary T cells: A practical guide,” dated Jun. 19, 2018. Retrieved from https://peerj.com/preprints/26993.html.
[cited by applicant]
Al-Lazikani et al., “Standard conformations for the canonical structures of immunoglobulins,” J Mol Biol (1997) 273(4):927-948.
[cited by applicant]
Alonso-Camino et al., “CARbodies: Human Antibodies Against Cell Surface Tumor Antigens Selected From Repertoires Displayed on T Cell Chimeric Antigen Receptors,” Mol Ther Nucl Acids (2013) 2: e93.
[cited by applicant]
Anonymous, “Scientists helping scietists™ | WWW Optimization of Human T Cell Expansion Protocol: Effects of Early Cell Dilution,” (2018).
[cited by applicant]
Benson et al., “CS1-Directed monoclonal antibody therapy for multiple myeloma,” J Clin Oncol (2012) 30(16):2012-2015.
[cited by applicant]
Boris-Lawrie et al., “Recent advances in retrovirus vector technology,” Cur. Opin. Genet. Develop. (1993) 3:102-109.
[cited by applicant]
Brash et al., “Strontium phosphate transfection of human cells in primary culture: stable expression of the simian virus 40 large-T-antigen gene in primary human bronchial epithelial cells,” Mol. Cell Biol. (1987) 7: 20…
[cited by applicant]
Brentjens et al., “CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia,” Sci Transl Med. (2013) 5(177):177ra38.
[cited by applicant]
Brown et al., “Structure-Based Mutagenesis of the Human Immunodeficiency Virus Type 1 DNA Attachment Site: Effects on Integration and cDNA Synthesis,” J Viral (1999) 73(11):9011-9020.
[cited by applicant]
Burns et al., “Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells,” Proc. Natl. Acad. Sci. USA (1…
[cited by applicant]
Carlens et al., “Ex vivo T lymphocyte expansion for retroviral transduction: influence of serum-free media on variations in cell expansion rates and lymphocyte subset distribution,” Exp Hematol (2000) 28(10): 1137-1146.
[cited by applicant]
Cavaletti et al., “Chemotherapy-induced peripheral neurotoxicity,” Nat Rev Neurol (2010) 6(12):657-666.
[cited by applicant]
Cavalieri et al., “Human T lymphocytes transduced by lentiviral vectors in the absence of TCR activation maintain an intact immune competence,” Blood (2003) 102(2): 497-505.
[cited by applicant]
Chang et al., “Identification and selective expansion of functionally superior T cells expressing chimeric antigen receptors,” J Transl Med (2015) 13(1):161.
[cited by applicant]
Chervin et al., “Engineering higher affinity T cell receptors using a T cell display system,” J Immunol Methods. (2008) 339(2): 175-84.
[cited by applicant]
Cheson , “Staging and response assessment in lymphomas: the new Lugano classification,” Chin Clin Oncol (2015) 4(1):5.
[cited by applicant]
Cheson et al., “Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification,” J Clin Oncol (2014) 32(27):3059-3068.
[cited by applicant]
Chicaybam et al., “An efficient low cost method for gene transfer to T lymphocytes,” PLoS One (2013) 8(3): e60298.
[cited by applicant]
Chothia et al.,. “The outline structure of the T-cell alpha beta receptor,” EMBO J. (1988) 7(12): 3745-55.
[cited by applicant]
Chu et al., “CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma,” Leukemia (2014) 28(4):917-927.
[cited by applicant]
Clackson et al., “Making antibody fragments using phage display libraries,” Nature (1991) 352(6336):624-628.
[cited by applicant]
Cooper et al., “T-cell clones can be rendered specific for CD19: toward the selective augmentation of the graft-versus-B-lineage leukemia effect,” Blood. (2003) 101:1637-1644.
[cited by applicant]
Coustan-Smith et al., “Immunological detection of minimal residual disease in children with acute lymphoblastic leukaemia,” Lancet (1998) 351(9102):P550-554.
[cited by applicant]
Davila et al., “CD19 CAR-targeted T cells induce long-term remission and B Cell Aplasia in an immunocompetent mouse model of B cell acute lymphoblastic leukemia,” PLoS One (2013) 8(4): e61338.
[cited by applicant]
Davila et al., “Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia,” Science Translational Medicine (2014) 6(224):224ra25.
[cited by applicant]
De Felipe et al., “Targeting of proteins derived from self-processing polyproteins containing multiple signal sequences,” Trafic (2004) 5(8):616-626.
[cited by applicant]
De Felipe, “Skipping the co-expression problem: the new 2A “Chysel” technology,” Genetics Vaccines and Therapy (2004) 2:13.
[cited by applicant]
Dull, T. et al. (Nov. 1998) “A Third-Generation Lentivirus Vector with a Conditional Packaging System,” J. Viral. 72:8463-8471.
[cited by applicant]
Eisenhauer et al., “New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1),” EJC (2009) 45(2):P228-247.
[cited by applicant]
Engelman et al., “Multiple effects of mutations in human immunodeficiency virus type 1 integrase on viral replication,” J Viral (1995) 69(5):2729-2736.
[cited by applicant]
Entschladen et al., “Differential requirement of protein tyrosine kinases and protein kinase C in the regulation of T cell locomotion in three-dimensional collagen matrices,” J Immunol. (1997) 159(7): 3203-3210.
[cited by applicant]
Fedorov et al., “PD-1- and CTLA-4-Based Inhibitory Chimeric Antigen Receptors (iCARs) Divert Off-Target Immunotherapy Responses,” Sci Transl Medicine (2013) 5(215):215ra172.
[cited by applicant]
Foon et al., “Immunologic classification of leukemia and lymphoma,” Blood (1986) 68(1):1-31.
[cited by applicant]
Fraietta et al., “Biomarkers of Response to Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy in Patients with Chronic Lymphocytic Leukemia,” Blood (2016) 128(22):57.
[cited by applicant]
Friedl et al., “T lymphocyte locomotion in a three-dimensional collagen matrix: Expression and function of cell adhesion molecules,” J Immunol. (1995) 154: 4973-4985.
[cited by applicant]
Gardner et al., “Intent to treat leukemia remission by CD19CAR T cells of defined formulation and dose in children and young adults,” Blood (2017) 129(25):3322-3331.
[cited by applicant]
Garfall et al., “Posterior Reversible Encephalopathy Syndrome (PRES) after infusion of anti-Bcma CAR T cells (CART_BCMA) for multiple myeloma: Successful Treatment with Cyclophophamide,” Blood (2016) 128(22):5702.
[cited by applicant]
Gargett et al., “Different cytokine and stimulation conditions influence the expansion and immune phenotype of third-generation chimeric antigen receptor T cells specific for tumor antigen GD2,” Cytotherapy (2015) 17(4)…
[cited by applicant]
Ghobadi et al., “Chimeric antigen receptor T cell therapy for non-Hodgkin lymphoma,” Curr Res Transl Med (2018) 66(2):43-49.
[cited by applicant]
Grupp et al., “Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia,” N Engl J Med (2013) 368:1509-1518.
[cited by applicant]
Hallek et al., “Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1…
[cited by applicant]
Hermans et al., “The VITAL assay: a versatile fluorometric technique for assessing CTL- and NKT-mediated cytotoxicity against multiple targets in vitro and in vivo,” J Immunol Methods (2004) 285(1):25-40.
[cited by applicant]
Holler et al., “In vitro evolution of a T cell receptor with high affinity for peptide/MHC,” Proc Natl Acad Sci U S A. (2000) 97(10): 5387-5392.
[cited by applicant]
Holler et al., “TCRs with high affinity for foreign pMHC show self-reactivity,” Nat Immunol. Jan. 2003;4(1):55-62.
[cited by applicant]
Honegger et al., “Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool,” J Mol Biol (2001) 309(3):657-670.
[cited by applicant]
Huang et al., “DNA transposons for modification of human primary T lymphocytes,” Methods Mol Biol (2009) 506: 115-126.
[cited by applicant]
Hudecek et al., “Receptor affinity and extracellular domain modifications affect tumor recognition by ROR1-specific chimeric antigen receptor T cells,” Clin Cancer Res (2013) 19(12):3153-3164.
[cited by applicant]
Imadome, “The clinical condition and diagnosis of EBV-T/NK-LPD (CAEBV, EBV-HLH etc.),” [Rinsho Ketsueki] Japanese J Clin Hematol (2013) 54(10):1992-98. (Reference in Japanese).
[cited by applicant]
Imamoto et al., “Advantages of AlaGIn as an additive to cell culture medium: use with anti-CD20 chimeric antibody-producing Potelligent™ CHO cell lines,” Cytotechnology (2013) 65:135-143.
[cited by applicant]
Janeway et al., Immunobiology: The Immune System in Health and Disease, 3rd ED., Current Biology Publications (1997), p. 4:33.
[cited by applicant]
Johnson et al., “Imaging for Staging and Response Assessment in Lymphoma,” Radiology (2015) 276(2):323-338.
[cited by applicant]
Johnston, et al., “Biolistic transformation: microbes to mice,” Nature (1990) 346: 776-777.
[cited by applicant]
Jores et al., “Resolution of hypervariable regions in T-cell receptor beta chains by a modified Wu-Kabat index of amino acid diversity.,” PNAS (1990) 87(23):9138-9142.
[cited by applicant]
Kindt et al., “Antigens and Antibodies,” in Chapter 4 of Kuby Immunology, 6th ed., W.H. Freeman and Co., N.Y, (2007) pp. 91, 14 pages.
[cited by applicant]
Klebanoff et al., “Sorting through subsets: which T-cell populations mediate highly effective adoptive immunotherapy?,” J Immunother. (2012) 35(9): 651-660.
[cited by applicant]
Kochenderfer et al., “B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells,” Blood (2012) 119(12):2709-2720.
[cited by applicant]
Kochenderfer et al., “Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor,” J. Immunotherapy (2009) 32(7): 689-702.
[cited by applicant]
Kochenderfer et al., “Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors,” Nature Reviews Clinical Oncology (2013) 10:267-276.
[cited by applicant]
Koste et al., “T-cell receptor transfer into human T cells with ecotropic retroviral vectors,” Gene Therapy (2014) 21: 533-538.
[cited by applicant]
Kotb, “Bacterial pyrogenic exotoxins as superantigens,” Clin Microbiol Rev. (1995) 8(3):411-426.
[cited by applicant]
Kurucz et al., “A bacterially expressed single-chain Fv construct from the 2B4 T-cell receptor,” Proc Natl Acad Sci U S A. (1993) 90(9): 3830-3834.
[cited by applicant]
Lada et al., “Quantitation of integrated HIV provirus by pulsed-field gel electrophoresis and droplet digital PCR,” J Clin Microbiol (2018) 56(12):e01158.
[cited by applicant]
Lee et al., “T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial.” The Lancet (2015) 385(9967) : 517-528.
[cited by applicant]
Lefranc et al., “IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains,” Dev Comp Immunol (2003) 27(1):55-77.
[cited by applicant]
Li et al., “Comparison of anti-CD3 and anti-CD28-coated beads with soluble anti-CD3 for expanding human T cells: Differing impact on CD8 T cell phenotype and responsiveness to restimulation,” J Transl Med (2010) 8(1):10…
[cited by applicant]
Li et al., “Comparison of inlet geomery in microfluidic cell affinity chromatography,” Analytical chemistry (2011) 83(3):774-781.
[cited by applicant]
Li et al., “Negative enrichment of target cells by microfluidic affinity chromatography,” Analytical Chemistry (2011) 83(20):7863-7869.
[cited by applicant]
Ling et al., “B-cell and plasma cell antigens: new and previously defined clusters,” Leucocyte typing III. (1987) 302-355.
[cited by applicant]
Liu et al., “Inclusion of Strep-tag II in design of antigen receptors for T-cell immunotherapy,” Nature Biotechnology (2016) 34(4):430-434.
[cited by applicant]
Lu et al., “A Rapid Cell Expansion Process for Production of Engineered Autologous CAR-T Cell Therapies,” Human Gene Therapy Methods (2016) 27(6):209-218.
[cited by applicant]
MacCallum et al., “Antibody-antigen interactions: contact analysis and binding site topography,” J Mol Biol (1996) 262(5):732-745.
[cited by applicant]
Manuri et al., “piggyBac transposon/transposase system to generate CD19-specific T cells for the treatment of B-lineage malignancies,” Hum Gene Ther (2010) 21(4): 427-437.
[cited by applicant]
Maude et al., “Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia,” New Engl J Med (2018) 378(5):439-448.
[cited by applicant]
Martin et al., “Modeling antibody hypervariable loops: a combined algorithm,” PNAS (1989) 86(23):9268-9272.
[cited by applicant]
McWilliams et al., “Mutations in the 5′ end of the human immunodeficiency virus type 1 polypurine tract affect RNase H cleavage specificity and virus titer,” J Viral (2003) 77(20):11150-11157.
[cited by applicant]
Miller et al., “Improved retroviral vectors for gene transfer and expression,” BioTechniques (1989) 7:980-990.
[cited by applicant]
Miller et al., “Retrovirus packaging cells,” Human Gene Therapy (1990) 1:5-14.
[cited by applicant]
Miyoshi et al. “Development of a self-inactivating lentivirus vector,” J Viral (1998) 72(10):8150-8157.
[cited by applicant]
Naldini et al., “In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector,” Science. Apr. 12, 1996;272(5259):263-7.
[cited by applicant]
Naldini et al., “Lentiviruses as gene transfer agents for delivery to non-dividing cells”, Curr Opin Biotechnol., Oct. 9, 1998; 5:457-63.
[cited by applicant]
Neeson et al., “Ex vivo culture of chimeric antigen receptor T cells generates functional CD8+ T cells with effector and central memory-like phenotype,” Gene Therapy (2010) 17(9):1105-1116.
[cited by applicant]
Okamoto et al., “A promising vector for TCR gene therapy: differential effect of siRNA, 2A peptide, and disulfide bond on the introduced TCR expression,” Mol Ther Nucl Acids (2012) 1(12):1-11.
[cited by applicant]
Park et al., “Treating cancer with genetically engineered T cells,” Trends Biotechnol. (2011) 29(11): 550-557.
[cited by applicant]
Philpott et al., “Use of Nonintegrating Lentiviral Vectors for Gene Therapy,” Human Gene Therapy (2007) 18:483.
[cited by applicant]
Portolano et al., “Lack of promiscuity in autoantigen-specific H and L chain combinations as revealed by human H and L chain “roulette”,” J Immunol (1993) 150(3):880-887.
[cited by applicant]
Powell et al., “Sequence and structural determinants required for priming of plus-strand DNA synthesis by the human immunodeficiency virus type 1 polypurine tract,” J Viral (1996) 70(8):5288-5296.
[cited by applicant]
Pullagurla et al., “Parallel affinity-based isolation of leukocyte subsets using microfluidics: application for stroke diagnosis,” Analytical chemistry (2014) 86(8):4058-4065.
[cited by applicant]
Ramsborg et al., “JCAR017 Is a Defined Composition CAR T Cell Product with Product and Process Controls That Deliver Precise Doses of CD4 and CD8 Car T Cell to Patients with NHL”, Blood (Dec. 7, 2017) 130(Issue Suppleme…
[cited by applicant]
Ramsborg et al., “JCAR017 Is a Defined Composition CAR T Cell Product with Product and Process Controls That Deliver Precise Doses of CD4 and CD8 Car T Cell to Patients with NHL”, Poster 4471 Presentation at 2017 Americ…
[cited by applicant]
Rosenberg, et al., “Cell transfer immunotherapy for metastatic solid cancer—what clinicians need to know,” Nat Rev Clin Oncol. (2011) 8(10):577-85.
[cited by applicant]
Sadelain et al., “The basic principles of chimeric antigen receptor design,” Cancer Discov. (2013) 3(4): 388-398.
[cited by applicant]
Scarpa et al., “Characterization of recombinant helper retroviruses from Moloney-based vectors in ecotropic and amphotropic packaging cell lines,” Virology (1991) 180:849-852.
[cited by applicant]
Schlueter et al., “Specificity and Binding Properties of a Single-chain T Cell Receptor,” J Mol Biol (1996) 859-869.
[cited by applicant]
Schuler et al., SYFPEITHI, Database for Searching and T-Cell Epitope Prediction. in Immunoinformatics Methods in Molecular Biology, (2007) 409(1): 75-93.
[cited by applicant]
Sharma et al., “Efficient sleeping beauty DNA transposition from DNA minicircles,” Molec Ther Nucl Acids (2013) 2, e74.
[cited by applicant]
Singh et al., “ProPred: prediction of HLA-DR binding sites,” Bioinformatics. (2001) 17(12): 1236-1237.
[cited by applicant]
Singh et al., “Early memory phenotypes drive T cell proliferation in patients with pediatric malignancies,” Sci Transl Med (2016) 8(320):320ra3.
[cited by applicant]
Soman et al., “MTS dye based colorimetric CTLL-2 cell proliferation assay for product release and stability monitoring of interleukin-15: assay qualification, standardization and statistical analysis,” J Immunol Methods…
[cited by applicant]
Soo Hoo et al., “Characterization of a single-chain T-cell receptor expressed in
[cited by applicant]
Stemberger et al., “Novel Serial Positive Enrichment Technology Enables Clinical Multiparameter Cell Sorting,” PLoS One (2012) 7(4): e35798.
[cited by applicant]
Tai et al., “Antibody-Based Therapies in Multiple Myeloma,” Bone Marrow Research (2010) vol. 2011. Article ID 924058.
[cited by applicant]
Terakura et al., “Generation of CD19-chimeric antigen receptor modified CD8+ T cells derived from virus-specific central memory T cells,” Blood (2012) 1:72-82.
[cited by applicant]
Themeli et al., “Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy,” Nat Biotechnol. (2013) 31(10): 928-933.
[cited by applicant]
Tsukahara et al., “CD19 target-engineered T-cells accumulate at tumor lesions in human B-cell lymphoma xenograft mouse models,” Biochem Biophys Res Commun (2013) 438(1): 84-89.
[cited by applicant]
Turtle et al., “Anti-CD19 Chimeric Antigen Receptor-Modified T Cell Therapy for B Cell Non- Hodgkin Lyphoma and Chronic Lyphocytic Leukemia: Fludarabine and Cyclophosphamide Lyphodepletion Imprives In Vivo Expansion and…
[cited by applicant]
Turtle et al., “CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients,” J. Clin. Invest. (2016) 126(6):2123-38.
[cited by applicant]
Turtle et al., “Engineered T cells for anti-cancer therapy,” Curr. Opin. Immunol. (2012) 24(5): 633-39.
[cited by applicant]
Turtle et al., “Immunotherapy of non-Hodgkin's lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells,” Sci Transl Med (2016) 8(355):355ra116.
[cited by applicant]
Van Tendeloo et al., “High-level transgene expression in primary human T lymphocytes and adult bone marrow CD34+ cells via electroporation-mediated gene delivery,” Gene Therapy (2000) 7(16): 1431-1437).
[cited by applicant]
Verhoeyen et al., “Lentiviral vector gene transfer into human T cells,” Methods Mol Biol. (2009) 506: 97-114.
[cited by applicant]
Vormittag et al., “A guide to manufacturing CAR T cell therapies,” Curr Opin in Biotechnology (2018) 53:164-181.
[cited by applicant]
Wadhwa et al., “Receptor mediated glycotargeting,” J. Drug Targeting (1995) 3: 111.
[cited by applicant]
Wadhwa et al., “Strategies for detection, measurement and characterization of unwanted antibodies induced by therapeutic biologicals,” J Immunol Methods (2003) 278(1-2):1-17.
[cited by applicant]
Wang et al., “Clinical manufacturing of CAR T cells: foundation of a promising therapy,” Molecular Therapy—Oncolytics (2016) 3:16015.
[cited by applicant]
Wang et al., “Phenotypic and functional attributes of lentivirus-modified CD19-specific human CD8+ central memory T cells manufactured at clinical scale,” J Immunother. (2012) 35(9):689-701.
[cited by applicant]
Wang et al., “Open-tubular capillary cell affinity chromatography: single and tandem blood cell separation,” Anal Chem (2008) 80(6):2118-2124.
[cited by applicant]
Wu et al., “Adoptive T-cell therapy using autologous tumor-infiltrating lymphocytes for metastatic melanoma: current status and future outlook,” Cancer (2012) 18(2): 160-175.
[cited by applicant]
Wulfing et al., “Correctly folded T-cell receptor fragments in the periplasm of
[cited by applicant]
Xu et al., “Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15,” Blood (2014) 123(24):3750-3759.
[cited by applicant]
Xu et al., “Cytokine release syndrome in cancer immunotherapy with chimeric antigen receptor engineered T cells,” Cancer Letters (2014) 343(2):172-178.
[cited by applicant]
Xu et al., “Multiparameter comparative analysis reveals differential impacts of various cytokines on CART cell phenotype and function ex vivo and in vivo,” Oncotarget (2016) 7(50):82354-82368.
[cited by applicant]
Yarilin, “Immunology principles,” M. Medicine (1999) 184-195, 339-347 (English Translation included).
[cited by applicant]
Zhao et al., “Development of the First World Health Organization Lentiviral Vector Standard: Toward the production control and standardization of lentivirus-based gene therapy products,” Human Gene Therapy Methods (2017…
[cited by applicant]
Zufferey et al. “Self-Inactivating Lentivirus Vector for Safe and Efficient In Vivo Gene Delivery,” J. Viral (1998) 72(12):9873-9880.
[cited by applicant]
Zufferey et al., “Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo,” Nat Biotechnol. Sep. 1997;15(9):871-875.
[cited by applicant]
U.S. Appl. No. 17/794,245, filed Jan. 22, 2021, by Germeroth et al.
[cited by applicant]
U.S. Appl. No. 17/850,875, filed Jun. 27, 2022, by Ramsborg et al.
[cited by applicant]
U.S. Appl. No. 17/846,868, filed Jun. 22, 2022, by Albertson et al.
[cited by applicant]
Applikon Biotechnology/BioPharma-Reporter (2016) How automation has changed the way we count cells BioPharma-Reporter.com; 1-4 (Year: 2016).
[cited by applicant]
Casati et al., “Clinical-scale selection and viral transduction of human naïve and central memory CD8+ T cells for adoptive cell therapy of cancer patients,” Cancer Immunology (2013) 62(10): 1563-1573.
[cited by applicant]
Church et al., “Tumor-specific CD4+ T cells maintain effector and memory tumor-specific CD8+ T cells,” Eur J Immunol (2014) 44: 69-79.
[cited by applicant]
Eaker et al., “Concise review: guidance in developing commercializable autologous/patient-specific cell therapy manufacturing,” Stem Cells Transl Med. (2013) 2(11): 871-83.
[cited by applicant]
Fraietta et al., “Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia,” Nat Med. (May 2018) 24(5):563-571. Epub Apr. 30, 2018.
[cited by applicant]
Franke et al., “Antibodies against CD20 or B-cell receptor induce similar transcription patterns in human lymphoma cell lines,” PLoS One.(2011) 6(2): e16596.
[cited by applicant]
Frayer et al., “Mean Body Weight, Height, Waist Circumference, and Body Mass Index Among Adults: United States, 1999-2000 Through 2015-2016,” Natl Health Stat Report. (2018) (122):1-16.
[cited by applicant]
Gearing et al., “The international standard for human interleukin-2. Calibration by international collaborative study,” J Immunological Methods (1988) 114(1-2):3-9.
[cited by applicant]
Gunzer et al,, “Two-step negative enrichment of CD4+ and CD8+ T cells from murine spleen via nylon wool adherence and an optimized antibody cocktail,” J Immunol Methods. (2001) 258(1-2): 55-63.
[cited by applicant]
Hudecek et al., “The nonsignaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity,” Cancer Immunol Res (2015) 3(2):125-135.
[cited by applicant]
Hunziker et al., “Exhaustion of cytotoxic T cells during adoptive immunotherapy of virus carrier mice can be prevented by B cells or CD4+ T cells,” Eur J Immunol (2002) 32(2):374-382.
[cited by applicant]
Janas et al., “Perfusion's role in maintenance of high-density T-cell cultures,” BioProcesses International. (2015) pp. 1-12.
[cited by applicant]
Kahn et al., “Optimization of retroviral vector-mediated gene transfer into endothelial cells in vitro,” Circ Res. (1992) 71(6):1508-17.
[cited by applicant]
Klaver et al., “T Cell Maturation Stage Prior to and During GMP Processing Informs on CAR T Cell Expansion in Patients,” Front Immunol. (2016) 7:648.
[cited by applicant]
Larson et al., “Defined cell composition and precise control over JCAR017 dose enables identification of relationships between chimeric antigen receptor T cell product attributes, pharmacokinetics, and clinical endpoint…
[cited by applicant]
Larson et al., “Defined cell composition and precise control over JCAR017 dose enables identification of relationships between chimeric antigen receptor T cell product attributes, pharmacokinetics, and clinical endpoint…
[cited by applicant]
Law et al., “What does it take to bind CAR?,” Mol Ther. (2005) 12(4):599-609.
[cited by applicant]
Li et al., “Directed evolution of human T-cell receptors with picomolar affinities by phage display,” Nature Biotechnology (2005) 23:349-354.
[cited by applicant]
Li et al., “Multiparameter cell affinity chromatography: Separation and analysis in a single microfluidic channel,” Anal Chem (2012) 84(19):8140-8148.
[cited by applicant]
Milone et al., “Chimeric Receptors Containing CD137 Signal Transduction Domains Mediate Enhanced Survival of T Cells and Increased Antileukemic Efficacy In Vivo,” Mol Ther (2009) 17(8):1453-64.
[cited by applicant]
Moeller et al., “Adoptive transfer of gene-engineered CD4+ helper T cells induces potent primary and secondary tumor rejection,” Blood (2005) 106(9):2995-3003.
[cited by applicant]
Nascimbeni et al., “Peripheral CD4+CD8+ T cells are differentiated effector memory cells with antiviral functions,” Blood (2004) 104(2):478-86.
[cited by applicant]
Skea et al., “The selective expansion of functional T cell subsets,” J Hematother Stem Cell Res. (1999) 8(5): 525-38.
[cited by applicant]
Sun et al., “Early transduction produces highly functional chimeric antigen receptor-modified virus-specific T-cells with central memory markers: a Production Assistant for Cell Therapy (PACT) translational application,…
[cited by applicant]
Turtle et al., “Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated With CD19-Specific Chimeric Antigen Receptor-Modified T Cells After Failure of Ibrutinib,” J Clin Oncol. (2017) 35(26): 3010-3020.
[cited by applicant]
U.S. Appl. No. 18/166,447, filed Feb. 8, 2023, by Ramsborg et al.
[cited by applicant]
Berthois et al., “Phenol red in tissue culture media is a weak estrogen: implications concerning the study of estrogen-responsive cells in culture,” Proc Natl Acad Sci U S A. (1986);83(8):2496-500.
[cited by applicant]
Carpenter et al., “B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma,” Clin Cancer Res. (2013) 19:2048-2060.
[cited by applicant]
Cheadle et al., “Chimeric antigen receptors for T-cell based therapy,” Methods Mol Biol (2012) 907:645-666.
[cited by applicant]
Cho et al., “Human mammalian cell sorting using a highly integrated micro-fabricated fluorescence-activated cell sorter (μFACS),” Lab on a Chip (2010) 10:1567-1573.
[cited by applicant]
Cohen et al., “Recognition of Fresh Human Tumor by Human Peripheral Blood Lymphocytes Transduced with a Bicistronic Retroviral Vector Encoding a Murine Anti-p53 TCR,” J Immunol (2005) 175(9):5799-5808.
[cited by applicant]
Darling et al., “Kinetic exclusion assay technology: characterization of molecular interactions,” Assay Drug Dev Technol. (2004) 2:647-657.
[cited by applicant]
Dimopoulos et al., “Current treatment landscape for relapsed and/or refractory multiple myeloma,” Nat Rev Clin Oncol. (2015) 12:42-54.
[cited by applicant]
Ex-Cell 302. Material Safety Data Sheet. SAFC Bioscience. p. 1-2. (Year: 2006).
[cited by applicant]
Fan et al., “Durable remissions with BCMA-specific chimeric antigen receptor (CAR)-modified T cells in patients with refractory/relapsed multiple myeloma,” Journal of Clinical Oncology (2017) 35(18_suppl): LBA3001-LBA30…
[cited by applicant]
Frecha et al., “Advances in the field of lentivector-based transduction of T and B lymphocytes for gene therapy,” Mol Ther (2010) 18(10):1748-1757.
[cited by applicant]
Garfall et al., “Immunotherapy with chimeric antigen receptors for multiple myeloma,” Discov Med (2014) 17(91):37-46.
[cited by applicant]
Gattinoni et al., “T memory stem cells in health and disease,” Nat Med (2017), 23: 18-27.
[cited by applicant]
GlutaMAX-1. Gibco. p. 1 (Year: 2010).
[cited by applicant]
Godin et al., “Microfluidics and photonics for Bio-System-on-a-Chip: A review of advancements in technology towards a microfluidic flow cytometry chip,” J Biophotonics (2008) 1(5):355-376.
[cited by applicant]
Hackett et al., “A transposon and transposase system for human application,” Molecular Therapy: The Journal of the American Society of Gene Therapy (2010) 18:674-683.
[cited by applicant]
Howarth et al., “A monovalent streptavidin with a single femtomolar biotin binding site,” Nature Methods (2006) 3:267-273.
[cited by applicant]
Imadome, “The clinical condition and diagnosis of EBV-T/NK-LPD (CAEBV, EBV-HLH etc.),” [Rinsho Ketsueki] Japanese J Clin Hematol (2013) 54(10):1992-98. (Reference in Japanese) English Tranlsation provided.
[cited by applicant]
Irving et al., “Engineering Chimeric Antigen Receptor T-Cells for Racing in Solid Tumors: Don't Forget the Fuel,” Front Immunol. (Apr. 3, 2017) 8:267.
[cited by applicant]
Jeon et al. Development of a serum-free medium for in vitro expansion of human cytotoxic T lymphocytes using a statistical design. BMC Biotechnology 2010, 10:70. p. 1-9 (Year: 2010).
[cited by applicant]
Jethwa et al., “Use of gene-modified regulatory T-cells to control autoimmune and alloimmune pathology: is now the right time?,” Clin Immunol. (2014) 150(1):51-63.
[cited by applicant]
Karnieli et al. A consensus introduction to serum replacements and serum-free media for cellular therapies. Cytotherapy, 2017; 19: 155-169 (Year: 2017).
[cited by applicant]
Katz et al., “Therapeutic targeting of CD19 in hematological malignancies: past, present, future and beyond.” Leuk Lymphoma. (2014) 55(5):999-1006.
[cited by applicant]
Klebanoff et al., “IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells,” Proc Natl Acad Sci USA (2004) 101: 1969-74.
[cited by applicant]
Lee et al., “Current concepts in the diagnosis and management of cytokine release syndrome,” Blood (2014) 124(2):188-195.
[cited by applicant]
Life Technologies Corporation (2013) OpTmizerTMCTSTMT-cell Expansion SFM Technical information; pp. 1-2 (Year: 2013).
[cited by applicant]
Lim et al., “Engineered streptavidin monomer and dimer with improved stability and function,” Biochemistry (2010) 50:8682-8691.
[cited by applicant]
Lupton et al., “Dominant positive and negative selection using a hygromycin phosphotransferase-Thymidine kinase dusion gene,” Molecular and cellular biology (1991) 11(6):3374-3378.
[cited by applicant]
Mak et al., “Glutathione Primes T Cell Metabolism for Inflammation,” Immunity. (2017) 46(4):675-689.
[cited by applicant]
Makita et al., “Clinical development of anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma,” Cancer Sci. Jun, 2017; 108(6):1109-1118.
[cited by applicant]
Mei et al., “Rationale of anti-CD19 immunotherapy: an option to target autoreactive plasma cells in autoimmunity,” Arthritis Res Ther. (2012) 14 Suppl 5(Suppl 5):S1.
[cited by applicant]
Navarro et al., “Estrogen Stimulation Differentially Impacts Human Male and Female Antigen-Specific T Cell Anti-Tumor Function and Polyfunctionality,” Gender and the Genome. (2017) 1:4, 167-179.
[cited by applicant]
Okern et al.,, “CTS™ immune cell SR for serum free culture and expansion of human T cells,” J Immunother Cancer. (2015); 3(Suppl 2): P1.
[cited by applicant]
Riddell et al., “The Fred Hutchinson Cancer Research Center and the University of Washington School of Medicine, Department of Medicine, Division of Oncology Oct. 7, 1991,” Human Gene Therapy (1992) 3:319-338.
[cited by applicant]
RPMI-1640 medium. Sigma-Aldrich. p. 1-2 (Year: 2007).
[cited by applicant]
Siddiqi et al., “Rapid MRD-Negative Responses in Patients with Relapsed/Refractory CLL Treated with Liso-Cel, a CD19-Directed CAR T-Cell Product: Preliminary Results from Transcend CLL 004, a Phase 1/2 Study Including P…
[cited by applicant]
Smith et al., “Ex vivo expansion of human T cells for adoptive immunotherapy using the novel xeno-free CTS immune cell serum replacement,” Clin Transl Immunol (2015) 4:e31.
[cited by applicant]
Sun et al., “Defective CD8 T cell memory following acute infection without CD4 T cell help,” Science (2003) 300: 339-42.
[cited by applicant]
Tai et al., “Targeting B-cell maturation antigen in multiple myeloma,” Immunotherapy (2015) 7:1187-1199.
[cited by applicant]
Technical Bulletin. Animal-Component Free Recombinant Human Insulin is Suitable for Use in Serum-Free Media. SAFC Bioscience. p. 1-4 (Year: 2006).
[cited by applicant]
Tran et al., “Minimally cultured tumor-infiltrating lymphocytes display optimal characteristics for adoptive cell therapy,” J Immunother (2008) 31: 742-51.
[cited by applicant]
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