IP Library Granted Patent US 12,275,787
Granted Patent B2
US 12,275,787 · App. 16/626,233 · Granted Apr 15, 2025

Chimeric antigen receptors (CARs), compositions and methods thereof

Inventors: Yupo Ma (Stony Brook, NY); Kevin Pinz (Stony Brook, NY); Xun Jiang (Stony Brook, NY); Masayuki Wada (Stony Brook, NY); Kevin Chen (Stony Brook, NY)
Assignee: iCell Gene Therapeutics LLC
C07K16/2803A61K39/4611A61K39/4613A61K39/4631A61K39/464402A61K39/464411A61K39/464412A61K39/464413A61K39/464417A61K39/464424A61K39/46444A61K39/464463A61K39/464471A61P35/00A61P35/02A61P37/06C07K14/5443C07K14/7051C07K14/70517C07K14/70578C07K16/2812C07K16/2866C07K16/3061C12N5/0636A61K38/00A61K2039/505A61K2239/28A61K2239/31A61K2239/38A61K2239/48C07K16/28C07K16/2887C07K16/289C07K16/2896C07K2317/622C07K2317/73C07K2319/02C07K2319/03C07K2319/74
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Quick Facts
Patent No.
US 12,275,787
App. No.
16/626,233
Granted
Apr 15, 2025
Kind
B2
Abstract

The present disclosure provides chimeric antigen receptors, compostions, and methods thereof. In one embodiment the present disclosure provides a method of treating autoimmune diseases, asthma, and preventing or mediating organ rejection in a subject.

Claims (5)

1. A method for treating an autoimmune disease, said method comprising administering to a patient in need thereof an ex vivo engineered T cell or NK cell co-expressing two distinct chimeric antigen receptor (CAR) units at the cell surface, wherein the engineered T cell or NK cell comprises a nucleotide sequence comprising from 5′ to 3′ a nucleotide encoding a promoter selected from human elongation factor-1 alpha (EF-1α) or spleen focus forming virus (SFFV), a first polynucleotide encoding a first chimeric antigen receptor polypeptide (CAR), a nucleotide encoding a first cleavage peptide, and a second polynucleotide encoding a second chimeric antigen receptor polypeptide (CAR), wherein the engineered cell further comprises a nucleotide encoding secreted IL-15/IL-15sushi or a functional fragment thereof, wherein the nucleotide encoding said enhancer is attached to the nucleotide encoding the first CAR or the nucleotide encoding the second CAR by a nucleotide encoding a second cleavage peptide that flanks either end of the two distinct encoded CAR units, wherein:

the first CAR comprises a first signal peptide, a first antibody binding domain, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and

the second CAR comprises a second signal peptide, a second antibody binding domain, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; and

wherein the first antibody binding domain and the second antibody binding domain are different and each bind to a different target, wherein the targets of the first and second antibody binding domains irrespective of order are CD19 and BMCA (CD269), wherein the first and second co-stimulatory domains are intracellular, and wherein the first and second cleavage peptides are selected from the group consisting of porcine teschovirus-1 2A (P2A), thoseaasigna virus 2A (T2A), equine rhinitis A virus (ERAV) 2A (E2A), and FMDV 2A (F2A), and wherein said autoimmune disease is systemic lupus erythematosus (SLE).

2. The method according to claim 1 , wherein the co-stimulatory domain is CD28.

Assignments (2)
MERGER AND CHANGE OF NAME Recorded Mar 6, 2025
From: ICELL GENE THERAPEUTICS, LLC; ICELL GENE THERAPEUTICS INC.
To: ICELL GENE THERAPEUTICS INC.
Reel/Frame 070420/0412 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 15, 2020
From: MA, YUPO; PINZ, KEVIN; JIANG, XUN; WADA, MASAYUKI; CHEN, KEVIN
To: ICELL GENE THERAPEUTICS LLC
Reel/Frame 051518/0942 →
Continuity (3)
Continuation 15538620 · Jun 21, 2017
Provisional Application 62523147 · Jun 21, 2017
Related Publication 20200223918A1 · Jul 16, 2020
References Cited (197)
US 8399645B2 · Campana et al. · 2013 [cited by applicant]
US 9328156B2 · June et al. · 2016 [cited by applicant]
US 10117896B2 · Powell, Jr. et al. · 2018 [cited by applicant]
US 10196444B2 · Jarjour et al. · 2019 [cited by applicant]
US 10253086B2 · Bitter et al. · 2019 [cited by applicant]
US 10273280B2 · Yupo et al. · 2019 [cited by applicant]
US 10287354B2 · Brogdon et al. · 2019 [cited by applicant]
US 10457731B2 · Jarjour et al. · 2019 [cited by applicant]
US 10472613B2 · Duchateau et al. · 2019 [cited by applicant]
US 11173179B2 · Ma et al. · 2021 [cited by applicant]
US 20020009449A1 · Wallner et al. · 2002 [cited by applicant]
US 20030105000A1 · Pero et al. · 2003 [cited by applicant]
US 20030147865A1 · Salomon et al. · 2003 [cited by applicant]
US 20040265315A1 · Dingivan et al. · 2004 [cited by applicant]
US 20050277587A1 · Chen et al. · 2005 [cited by applicant]
US 20080254027A1 · Bernett et al. · 2008 [cited by applicant]
US 20080254512A1 · Capon · 2008 [cited by applicant]
US 20080299042A1 · Bechtel et al. · 2008 [cited by applicant]
US 20090081157A1 · Kornbluth et al. · 2009 [cited by applicant]
US 20090238791A1 · Jacques et al. · 2009 [cited by applicant]
US 20090325188A1 · Glass · 2009 [cited by applicant]
US 20100331527A1 · Davis et al. · 2010 [cited by applicant]
US 20120058082A1 · Kaplan et al. · 2012 [cited by applicant]
US 20120070408A1 · Kaplan · 2012 [cited by applicant]
US 20120134970A1 · Yang et al. · 2012 [cited by applicant]
US 20120258494A1 · Stitz · 2012 [cited by applicant]
US 20130058936A1 · Bruenker et al. · 2013 [cited by applicant]
US 20130259876A1 · Murphy et al. · 2013 [cited by applicant]
US 20130287748A1 · June et al. · 2013 [cited by applicant]
US 20130287752A1 · Davila et al. · 2013 [cited by applicant]
US 20140044641A1 · Toporik et al. · 2014 [cited by applicant]
US 20140099309A1 · Powell, Jr. et al. · 2014 [cited by applicant]
US 20140106449A1 · June et al. · 2014 [cited by applicant]
US 20140286918A1 · Dao · 2014 [cited by applicant]
US 20140322183A1 · Milone et al. · 2014 [cited by applicant]
US 20150038684A1 · Jensen · 2015 [cited by applicant]
US 20150133640A1 · Blein et al. · 2015 [cited by applicant]
US 20150140019A1 · June et al. · 2015 [cited by applicant]
US 20150307623A1 · Abbot et al. · 2015 [cited by applicant]
US 20150342993A1 · Kloss et al. · 2015 [cited by applicant]
US 20160068601A1 · Brogdon et al. · 2016 [cited by applicant]
US 20160207989A1 · Short · 2016 [cited by applicant]
US 20160250258A1 · Delaney et al. · 2016 [cited by applicant]
US 20160297989A1 · Nimura et al. · 2016 [cited by applicant]
US 20160340406A1 · Zhao et al. · 2016 [cited by applicant]
US 20170145108A1 · Schreiber et al. · 2017 [cited by applicant]
US 20170267742A1 · Jensen et al. · 2017 [cited by applicant]
US 20180066034A1 · Yupo et al. · 2018 [cited by applicant]
US 20180162939A1 · Yupo et al. · 2018 [cited by applicant]
US 20180179280A1 · Png et al. · 2018 [cited by applicant]
US 20180187149A1 · Ma et al. · 2018 [cited by applicant]
US 20180371052A1 · Yupo et al. · 2018 [cited by applicant]
US 20190038733A1 · Campana et al. · 2019 [cited by applicant]
US 20190046571A1 · Campana et al. · 2019 [cited by applicant]
US 20190135894A1 · Yupo et al. · 2019 [cited by applicant]
US 20190255108A1 · Yupo et al. · 2019 [cited by applicant]
US 20190345217A1 · Ma et al. · 2019 [cited by applicant]
US 20200024342A9 · Ma et al. · 2020 [cited by applicant]
US 20200071397A1 · Dipersio et al. · 2020 [cited by applicant]
US 20200071399A1 · Jarjour et al. · 2020 [cited by applicant]
US 20200078399A1 · Fan et al. · 2020 [cited by applicant]
US 20200109364A1 · Dipersio et al. · 2020 [cited by applicant]
US 20200283534A1 · Ma et al. · 2020 [cited by applicant]
US 20200308541A1 · Ma et al. · 2020 [cited by applicant]
US 20200371091A1 · Pruteanu-Malinici et al. · 2020 [cited by applicant]
US 20220241327A1 · Ma et al. · 2022 [cited by applicant]
US 20220348633A1 · Ma et al. · 2022 [cited by applicant]
US 20230277622A1 · Ma et al. · 2023 [cited by applicant]
US 20230340113A1 · Ma et al. · 2023 [cited by applicant]
US 20240141041A1 · Ma et al. · 2024 [cited by applicant]
EP 3288940B1 · 2018 [cited by applicant]
WO WO2007046006A2 · 2007 [cited by examiner]
WO 2009091826A2 · 2009 [cited by applicant]
WO 2012079000A1 · 2012 [cited by applicant]
WO 2013123061A1 · 2013 [cited by applicant]
WO 2013126712A1 · 2013 [cited by applicant]
WO 2014055668A1 · 2014 [cited by applicant]
WO 2014100385A1 · 2014 [cited by applicant]
WO 2014124143A1 · 2014 [cited by applicant]
WO 2014127261A1 · 2014 [cited by applicant]
WO 2014145252A2 · 2014 [cited by applicant]
WO 2014184143A1 · 2014 [cited by applicant]
WO 2014186469A2 · 2014 [cited by applicant]
WO 2015018529A1 · 2015 [cited by applicant]
WO 2015075468A1 · 2015 [cited by applicant]
WO 2015075469A1 · 2015 [cited by applicant]
WO 2015075470A1 · 2015 [cited by applicant]
WO WO2015120180A1 · 2015 [cited by examiner]
WO WO2015121454A1 · 2015 [cited by examiner]
WO 2015157399A1 · 2015 [cited by applicant]
WO 2015168613A2 · 2015 [cited by applicant]
WO 2015172339A1 · 2015 [cited by applicant]
WO 2016011210A2 · 2016 [cited by applicant]
WO 2016014553A1 · 2016 [cited by applicant]
WO WO2016014565A2 · 2016 [cited by examiner]
WO 2016102965A1 · 2016 [cited by applicant]
WO 2016210293A1 · 2016 [cited by applicant]
WO 2017068361A1 · 2017 [cited by applicant]
Osborn et al. A Picornaviral 2A-Like Sequence-Based Tricistronic Vector Allowing for High-Level Therapeutic Gene Expression Coupled to a Dual-Reporter System. Molecular Therapy vol. 12, No. 3, Sep. 2005 (Year: 2005). [cited by examiner]
Szymczak et al.Correction of multi-gene deficiency in vivo using a single ‘self-cleaving’ 2A peptide-based retroviral vector. Nature Biotechnology vol. 22 No. 5 May 2004 (Year: 2004). [cited by examiner]
Hoyos et al. Engineering CD19 specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia (2010) 24, 1160-1170 (Year: 2010). [cited by examiner]
Lanitis et al .Optimized gene engineering of murine CAR-T cells reveals the beneficial effects of IL-15 co-expression. J. Exp. Med. 2020 vol. 218 No. 2 e20192203 (Year: 2019). [cited by examiner]
Qi et al_Interleukin-12 exacerbates Sjogren's syndrome through induction of myeloid-derived suppressor cells. Molecular Medicine RE POR TS 20: 1131-1138, 2019. (Year: 2019). [cited by examiner]
Liu, Fang, et al., “First-in-Human CLL1-CD33 Compound Car T Cell Therapy Induces Complete Remission in Patients with Refractory Acute Myeloid Leukemia: Update on Phase 1 Clinical Trial,” http://www.bloodjournal.org/cont… [cited by applicant]
John, Liza B., et al., “Anti-PD-1 Antibody Therapy Potently Enhances the Eradication of Established Tumors by Gene-Modified T Cells,” Clinical Cancer Research; 19, No. 20, pp. 5636-5646, Oct. 15, 2013. [cited by applicant]
Rowley, Jesse, et al., “Expression of IL-15RA or an IL-15/IL-15RA fusion on CD8+ T cells modifies adoptively transferred T-cell function in cis,” European Journal of Immunology, 39, No. 2: 491-506, 2009. [cited by applicant]
Gill, Saar, MD, Phd, “Chimeric Antigen Receptor T-Cell Therapy in AML: How Close are We?”, Best Practice & Research Clinical Haematology, Dec. 2016; 29(4): 329-333. doi:10.1016/j.beha.2016.10.004. [cited by applicant]
Chen, KH, et al., “A Compound Chimeric Antigen Receptor Strategy for Targeting Multiple Myelomac” Leukemia (2018) 32, 402-412. [cited by applicant]
Petrov, Jessica C., et al., “Compound CAR T-Cells as a Double-Pronged Approach for Treating Acute Myeloid Leukemia,” Leukemia (2018) 32: 1317-1326. [cited by applicant]
Hamieh, Mohamad, et al., “CAR T Cell Trogocytosis and Cooperative Killing Regulate Tumour Antigen Escape,” Nature 568, 112-116 (2019). [cited by applicant]
Qin, Haiying, et al., “Novel CD19/CD22 Bicistronic Chimeric Antigen Receptors Outperform Single or Bivalent Cars In Eradicating CD19+CD22+, CD19- and CD22-Pre-B Leukemia,” Blood 2017, 130:810. [cited by applicant]
Brown, et al., “Novel Treatments for Chronic Lymphocytic Leukemia and Moving Forward,” American Society of Clinical Oncology Educational Book, vol. 34, 2014, pp. e317-e325, XP055201368. [cited by applicant]
Leavitt, et al., “Concordant Modulation of Neutralization Resistance and High Infectivity of the Primary Human Immunodeficiency Virus Type 1 MN Strain and Definition of a Potential gp41 Binding Site,” gp120 Journal of V… [cited by applicant]
Schreiber, et al., “Cancer Immunoediting: Integrating Immunity's Roles in Cancer Suppression and Promotion,” pp. 1565-1570, Mar. 2011. [cited by applicant]
Marzo, et al., “Fully Functional Memory CDS T Cells in the Absence of CD4 T Cells,” Journal of Immunology, 173:969-975, 2004. [cited by applicant]
Moeller, et al., “Sustained Antigen-Specific Antitumor Recall Response Mediated by Gene-Modified CD4+ T Helper-1 and CDS+ T Cells,” Cancer Research 67, No. 23 :11428-11437, 2007. [cited by applicant]
Moeller,et al., “Adoptive Transfer of Gene-Engineered CD4 Helper T Cells Induces Potent Primary and Secondary Tumor Rejection,” Blood, vol. 106, No. 9, pp. 2995-3003, Nov. 2005. [cited by applicant]
Gibson, et al., “Risk of Non-Hodgkin Lymphoma Subtypes in HIV-Infected People During the HAART Era: A Population-Based Study,” AIDS, Sep. 24, 2014; 28(15): 2313-2318, London, England. [cited by applicant]
Beard, et al., “Multiple Chimeric Antigen Receptors Successfully Target Chondroitin Sulfate Proteoglycan 4 in Several Different Cancer Histologies and Cancer Stem Cells,” Journal for Immunotherapy of Cancer 2014; 2(25),… [cited by applicant]
Imboden, et al., “Stimulation of CDS Enhances Signal Transduction by the T Cell Antigen Receptor,” J. Clinical Investigation, 1990; 85:130-134. [cited by applicant]
Rabinowich, et al., “Signaling Via CD7 Molecules on Human NK Cells. Induction of Tyrosine Phosphorylation and Beta 1 Integrin-Mediated Adhesion to Fibronectin,” The Journal of Immunology, 1994; 153:3504-3513. [cited by applicant]
Inoue, et al., “Mechanisms of NK Cell Activation Stimulated by CD2; Granzyme B is Released by CD2 Crosslinking-Stimulation on NK92 Cells,” Journal of Osaka Dental University, Oct. 2012; 46(2): 229-235. [cited by applicant]
McNerney, et al., “The CD2 Family of Natural Killer Cell Receptors,” Immunobiology of Natural Killer Cell Receptors, Sprinter, Berlin, Heidelberg, 2006; 298:91-120. [cited by applicant]
Rabinowich, et al., “Expression and Function of CD7 Molecule on Human Natural Killer Cells,” Journal of Immunology, 1994; 152: 517-526. [cited by applicant]
Liu, et al., “Critical Role of CD2 Co-stimulation in Adaptive Natural Killer Cell Responses Revealed in NKG2CDeficient Humans,” Cell Reports 2016; 15, 1088-1099. [cited by applicant]
Muyldermans, et al., “Single Domain Camel Antibodies: Current Status,” Reviews in Molecular Biotechnology 74, No. 4, , (2001): pp. 277-301, 22001. 277302. [cited by applicant]
Muyldermans, et al., “Recognition of Antigens by Singledomain Antibody Fragments: The Superfluous Luxury of Paired Domains,” Trends in Biochemical Sciences, vol. 26, No. 4, pp. 230-235, Apr. 2001. [cited by applicant]
Grupp, et al., “Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia,” New England Journal of Medicine, Apr. 18, 2013, vol. 368, No. 16, pp. 1509-1518. [cited by applicant]
Rowley, et al., “Expression of IL-15RA or an IL-15/1L-15RA Fusion on CD8+ T Cells Modifies Adoptively Transferred T-Cellfunction in cis,” European Journal of Immunology, 2009, vol. 39, No. 2, pp. 491-506. [cited by applicant]
John et al., “Anti-PD-1 Antibody Therapy Potently Enhances the Eradication of Established Tumors By Gene-Modified T Cells,” Clinical Cancer Research, Oct. 15, 2013, vol. 19, No. 20, pp. 5636-5646. [cited by applicant]
Penney, et al., “Greater Frequency of CD5-Negative CD8(+) T Vells Against Human Immunodeficiency Virus Type 1 than Other Viruses is Consistent with Adaptation to Antigenic Variation,” AIDS Research and Therapy, Sep. 15,… [cited by applicant]
Maus, et al., “Antibody-Modified T Cells: CARs Take the Front Seat for Hematologic Malignancies,” Blood, Apr. 24, 2014, vol. 123, No. 17, pp. 2625-2635. [cited by applicant]
D'Amore, et al., “Phase II Trial of Zanolimumab (HuMax-CD4) in Relapsed or Refractory Non-Cutaneous Peripheral T Cell Lymphoma,” British Journal of Haematology, 150, No. 5, pp. 565-573, 2010. [cited by applicant]
Shenghui, et al., “Elevated Frequencies of CD4+CD25+CD127lo regulatory T Cells is Associated to Poor Prognosis in Patients with Acute Myeloid Leukemia,” International Journal of Cancer, 129 No. 6, pp. 1373-1381, 2011. [cited by applicant]
Ehninger et al., “Distribution and Levels of Cell Surface Expression of CD33 and CD123 in Acute Myeloid Leukemia,” Blood Cancer Journal 2014, vol. 4, pp. 1-10. [cited by applicant]
Liu, et al., “512. Tumor-Associated Macrophages Via Up-Regulation of PD1 Ligands Protect Neuroblastoma from Immunotherapy With NKT Cells Expressing GD2-Specific Chimeric Antigen Receptor,” Molecular Therapy 23 (2015): S… [cited by applicant]
Rouce, et al., “Equal Opportunity Car T cells,” Blood 2017, 129:3275-3277. [cited by applicant]
Lai, et al., “The Roles of CD4+ T Cells in Tumor Immunity,” ISRN Immunology, vol. 2011, Article ID 497397, 6 pages, DOI:10.5402/2011/497397. [cited by applicant]
Kebriaei, et al., “Phase I Trials Using Sleeping Beauty to Generate CD19-Specific Car T Cells,” The Journal of Clinical Investigation, vol. 126, No. 9, pp. 3363-3376 and Supplemental Tables, Sep. 2016. [cited by applicant]
Wilkie, et al., Dual Targeting of ErbB2 and MUC1 in Breast Cancer Using Chimeric Antigen Receptors Engineered to Provide Complementary Signaling, Journal of Clinical Immunology, (2012) 32:1059-1070. [cited by applicant]
Dotti, et al., “Design and Development of Therapies using Chimeric Antigen Receptor-Expressing T Cells,” Immunological Reviews, Jan. 2014; 257(1): pp. 1-35. [cited by applicant]
Curran, Kevin, et al., “Chimeric Antigen Receptors for T Cell Immunotherapy: Current Understanding and Future Directions.” The Journal of Gene Medicine, 14.(6), pp. 405-415, Jun. 2012. [cited by applicant]
Shirasu, N., et al., “Functional Design of Chimeric T-Cell Antigen Receptors for Adoptive Immunotherapy of Cancer: Architecture and Outcomes,” Anticancer Research, 32(6), pp. 2377-2384, 2012. [cited by applicant]
Bridgeman, J.S., et al., “CD 3ζ-Based Chimeric Antigen Receptors Mediate T Cell Activation Via Cis-and Trans-Signalling Mechanisms: Implications for Optimization of Receptor Structure for Adoptive Cell Therapy,” Clinica… [cited by applicant]
Kaiser, A.D., et al., “Towards a Commercial Process for the Manufacture of Genetically Modified T Cells for Therapy,” Cancer Gene Therapy, 22(2), pp. 72-78, Jan. 2015. [cited by applicant]
Sentman, C.L., “Challenges of Creating Effective CARs for Cancer Therapy,” Immunotherapy, 5(8), pp. 783-785, 2013. [cited by applicant]
Chen, C., et al., “Development of T Cells Carrying Two Complementary Chimeric Antigen Receptors Against Glypican-3 and Asialoglycoprotein Receptor 1 for the Treatment of Hepatocellular Carcinoma,” Cancer Immunology, Imm… [cited by applicant]
Mihara, K., et al., “T Cells Bearing Anti-CD19 and/or Anti-CD38 Chimeric Antigen Receptors Effectively Abrogate Primary Double-Hit Lymphoma Cells,” Journal of Hematology & Oncology 10, No. 1: 116-119, 2017. [cited by applicant]
Zhang, et al., Journal of Hematology & Oncology, 11:102-116, 2018. [cited by applicant]
Zhu, F., et al., “Closed-System Manufacturing of CD19 and Dual-Targeted CD20/19 Chimeric Antigen Receptor T Cells Using the CliniMACS Prodigy Device at an Academic Medical Center,” Cytotherapy 20, No. 3: 394-406, 2018. [cited by applicant]
Sommermeyer, D., et al., “Chimeric Antigen Receptor-Modified T Cells Derived from Defined CD8+ and CD4+ Subsets Confer Superior Antitumor Reactivity in Vivo,” Leukemia, 30(2): 492-500, Feb. 2016. [cited by applicant]
Aandahl, E. et al., “Expansion of CD7low and CD7negative CD8 T-Cell Effector Subsets in HIV-1 Infection: Correlation with Antigenic Load and Reversion by Antiretroviral Treatment,” Blood, vol. 104, No. 12, pp. 3672-3678… [cited by applicant]
Abate-Daga, et al., “CAR Models: Next-Generation CAR Modifications for Enhanced T-Cell Function,” Molecular Therapy-Oncolytics 3, Article 16014 (2016). [cited by applicant]
Amlot, P. et al., “Chapter 18 CD7 Monoclonal Antibodies—Therapeutic Monoclonal Antibodies,” pp. 287-288 (1990). [cited by applicant]
Arafat, Waleed, et al. “Antineoplastic Effect of Anti-ErbB-2 Intrabody is not Correlated with scFv Affinity for its Target,” Cancer Gene Therapy, vol. 7, No. 9, pp. 1250-1256 (2000). [cited by applicant]
Brentjens, Renier J., et al. “Eradication of Systemic B-Cell Tumors by Genetically Targeted Human T Lymphocytes Co-Stimulated by CD80 and Interleukin-15,” Nature Medicine. vol. 9, No. 3, pp. 279-286 (2003). [cited by applicant]
Burgess, Wilson H. et al., “Possible Dissociation of the Heparin-Binding and Mitogenic Activities of Heparin-Binding (Acidic Fibroblast) Growth Factor-1 from its Resceptor-Binding Activities by Site-Directed Mutagenesis… [cited by applicant]
Casset, Florence, et al., “A Peptide Mimetic of an Anti-CD4 Monoclonal Antibody by Rational Design,” BBRC, vol. 307, pp. 198-205 (2003). [cited by applicant]
Chen Yvonne, et al., “Selection and Analysis of an Optimized Anti-VDGG Antiobody: Crystal Structure of an Affinity-Matured Fab in Complex with Antigen,” J. Mol. Bio., vol. 293, pp. 865-881 (1999). [cited by applicant]
Colman, P. M. et al., “Effects of Amino Acid Sequence Changes on Antibody-Antigen Interactions,” Research in Immunology, vol. 145, No. 1, pp. 33-36 (1994). [cited by applicant]
De Pascalis, Roberto, et al., “Grafting of ‘Abbreviated’ Complementarity-Determining Regions Containing Specificity-Determining Residues Essential for Legand Contact to Engineer a Less Immunogenic Humanized Monoclonal A… [cited by applicant]
Esmaeilzadeh, Abdolreza et al: “Chimeric Antigen Receptor-T Cell Therapy: Applications and Challenges in Treatment of Allergy and Asthma,” Biomedicine and Pharmacotherapy, vol. 123, (2019). [cited by applicant]
Maus, Marcela V., et al. “Antibody-Modified T Cells: CARs Take the Front Seat for Hematologic Malignancies,” Blood, The Journal of the American Society of Hematology, vol. 123, No. 17, pp. 2625-2635 (2014). [cited by applicant]
Fehniger, Todd A., et al., “Fatal Leukemia In Interleukin 15 Trangenic Mice Follows EarlyExpansion in Natural Killer and Memory Phenotype CD8+ T Cells,” Journal of Exp. Med. Rockefeller Univ. Press, vol. 193, No. 2, pp.… [cited by applicant]
Almagro & Frans Son, “Humanization of Antibodies,” Frontiers in Bioscience vol. 13, pp. 1619-1633 (Jan. 1, 2008). [cited by applicant]
Glienke, Wolfgang, et al., “Advantages and Applications of CAR-Expressing Natural Killer Cells,” Frontiers in Pharmacology, vol. 6, Article 21 (Feb. 2015). [cited by applicant]
Guo, Yelei et al., “Efficiency and Side Effects of Anti-CD38 Car T Cells in an Adult Patient With Relapsed B-ALL After Failure of Bi-Specific CD19/CD22 Car T Cell Treatment,” Cellular & Molecular Immunology, vol. 17, pp… [cited by applicant]
Hegde, M et al. “Combinational Targeting Offsets Antigen Escape and Enhances Effector Functions of Adoptively Transferred T cells in Glioblastoma,” Molecular Therapy, vol. 21, No. 11, pp. 2087-2101 (2013). [cited by applicant]
Holm, Patrick, et al., “Functional Mapping and Single Chain Constructionof the Anti-Cytokeratin 8 Monoclonal Antibody TS1,” Molecular Immunology, vol. 44, pp. 1075-1084 (2002). [cited by applicant]
Hu, Qiyue, et al. “Discovery of a Novel IL-15 Based Protein with Improved Developability and Efficacy for Cancer Immunotherapy,” Scientific Reports, vol. 8, No. 1, p. 7675 (2018). [cited by applicant]
Hurton, Lenka V., et al., “Tethered IL-15 on CD19-Specific T Cells Sustains Long-Term Persistence and Promotes a Stem Cell Memory-Like Phenotype,” Molecular Therapy, Abstract 626, pages S242 (2014). [cited by applicant]
Jena, Bipulendu, et al., “Redirecting T-Cell Specificity by Introducing a Tumor-Specific Chimeric Antigen Receptor,” Blood, vol. 116, No. 7, pp. 1035-1044 (Aug. 2010). [cited by applicant]
Kang, Liqing, et al., “Characterization of Novel Dual Tandem CD19/BCMA Chimeric Antigen Receptor T Cells to Potentially Treat Muliple Myeloma,” Biomarker Research, vol. 8, No. 14 (2020). [cited by applicant]
Kershaw, Michael H. et al., “Redirected Cytotoxic Effector Function”, Journal of Biological Chemistry, vol. 271, No. 35, pp. 21214-21220 (Aug. 1996). [cited by applicant]
Lang, Peter, et al. “Chimeric CD19 Antibody Mediates Cytotoxic Activity Against Leukemic Blasts with Effector Cells from Pediatric Patients Who Received T-Cell-Depleted Allografts,” Blood, vol. 103, No. 10, pp. 3982-398… [cited by applicant]
Lemaistre, C.F., “Phase I Trial of H65-RTA Immunoconjugate in Patients With Cutaneous T-cell Lymphoma”, Blood, vol. 78, No. 5, pp. 1173-1182 (Sep. 1, 1991). [cited by applicant]
Leong, Steven R., et al., “An Anti-CD3/anti-CLL-1 Bispecific Antibody for the Treatment of Acute Myeloid Leukemia,” Blood, vol. 129, No. 5, pp. 609-618 (2017). [cited by applicant]
Ma, Jennifer S. Y., et al., “Versatile Strategy for Controlling the Specificity and Activity of Engineered T cells,” PNAS, pp. E450-#458 (2016). [cited by applicant]
MacCallum, Robert M., et al., “Antibody-Antigen Interactions: Contact Analysis and Binding Site Topography,” J. Mol. Biol., vol. 262, pp. 732-745 (1996). [cited by applicant]
Maude, S. L., et al., “Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia,” N. England Journal of Medicine, vol. 378, No. 5, pp. 439-446 (Feb. 1, 2018). [cited by applicant]
Milone, Michael C., et al., “Chimeric Receptors Containing CD137 Signal Transduction Domains Mediate Enhanced Survival of T. Cells and Increased Antileukemic Efficacy in Vivo,” Molecular Therapy vol. 17, No. 8, pp. 1453… [cited by applicant]
Moreaux, Jerome, et al., “BAFF and APRIL Protect Myeloma Cells from Apoptosis Induced by Interleukin 6 Deprivation and Dexamethasone”, Blood, vol. 103, No. 8, pp. 3148-4157 (Apr. 2004). [cited by applicant]
Phares, Timothy W., et al. “CD4 T Cells Promote CD8 T Cell Immunity at the Priming and Effector Site During Viral Encephalitis,” Journal of Virology, vol. 86, No. 5. pp, 2416-2427 (2012). [cited by applicant]
Png, Yi Tian, et al. “Blockade of CD7 Expression in T Cells for Effective Chimeric Antigen Receptor Targeting of T-Cell Malignancies,” Blood Advances, vol. 1, No. 25, pp. 2348-2360 (2017). [cited by applicant]
Ramos Carlos A., et al., “CD19-CAR Trials,” Cancer Journal, vol. 20, No. 2, pp. 112-118 (2014). [cited by applicant]
Rudikoff, Stuart et al., “Single amino acid substitution altering antigen-binding specificity” Proc Natl Acad Sci USA, vol. 79 pp. 1979-1983 (1982). [cited by applicant]
Ruella, Marco et al., “Dual CD19 and CD123 Targeting Prevents Antigen-Loss Relapses After CD19-Directed Immunotherapies,” Journal of Clinical Investigation, vol. 126, Nol 10, pp. 3814-3826 (2016). [cited by applicant]
Sahm, Christiane et al., “Expression of IL-15 in NK Ccells Results in Rapid Enrichment and Selective Cytotoxicity of Gene-Modified Effectors that Carry a Tumor-Specific Antigen Receptor,” Cancer Immunology, Immunotherap… [cited by applicant]
Sato, Noriko, et al., “Development of an IL-15-Autocrine CD8 T-cell Leukemia in IL-15-Transgenic Mice Requires the CIS Expression of IL-15R,” Blood, vol. 117, No. 15 pp. 4032-4040 (2018). [cited by applicant]
Skuljec, Jelena, et al., “Chimeric Antigen Receptor-Redirected Regulatory T Cells Suppress Experimental Allergic Airway Inflammation, a Model of Asthma,” Frontiers in Immunology, vol. 8, Article 1125 (Sep. 2017). [cited by applicant]
Vajdos, Felix F., et al.“Comprehensive Functional Maps of the Antigen-binding Site of an Anti-ErbB2 Antibody Obtained with Shotgun Scanning Mutagenesis,” J. Mol. Biol. Vol. 320, pp. 415-428 (2002). [cited by applicant]
Wang, Weijia, et al. “BCMA-CD19 Compound CAR T Cells for Systemic Lupus Erythematosus: A Phase 1 Open-Label Clinical Trial,” Annals of the Rheumatic Diseases, vol. 83, No. 10 (Abstract) (2024). [cited by applicant]
Ward, Dana E., et al. “Chimeric Antigen Receptors Based on Low Affinity Mutants of FcϵRI Re-Direct T Cell Specificity to Cells Expressing Membrane IgE,” Frontiers in Immunology, vol. 9, Article 2231 (2018). [cited by applicant]
Wilkie et al., “Selective Expansion of Chimeric Antigen Receptor-Targeted T-Cells with Potent Effector Function Using Interleukin-4,” Journal of Biological Chemistry, vol. 285, No. 33, pp. 25538-25544 (2010). [cited by applicant]
Chen, et al., “CD7 Nanobody-Derived Anti-CD7 Chimeric Antigen Receptor T-Cells Exhibited Potent Antitumor Activities to CD7 Positive Malignancies,” (HemaSphere, vol. 4, Supp 1, pp. 100-101, Abstract No. S277, (English A… [cited by applicant]
Fan et al., “The Killing Activity of a CD7 Nanobody Derived CAR-T Cells on CD7 Positive Acute Myeloid Leukemia Cells,” Chinese Journal of Cancer Biotherapy, vol. 27, No. 8, pp. 852-859, English Abstract from EMBASE (Aug… [cited by applicant]
Mortier, Erwan, et al., “Soluble Interleukin-15 Receptor Alpha (IL-15Ralpha)-Sushi as a Selective and Potent Agonist of IL-15 Action through IL-15Rb/y;” Journal of Biological Chemistry, vol. 281, No. 3, pp. 1612-1619 (2… [cited by applicant]