IP Library Granted Patent US 12,303,551
Granted Patent B2
US 12,303,551 · App. 17/040,472 · Granted May 20, 2025

Cellular immunotherapy compositions and uses thereof

Inventor: Daniel Mark Corey (Menlo Park, CA)
Assignee: Cero Therapeutics Holdings, Inc.
A61K38/1774A61K35/17A61K38/177A61K40/11A61K40/24A61K40/32A61K40/42A61K40/46A61K45/06A61P35/00A61P37/04C07K14/70503C07K14/7051C07K14/70578C07K14/70596C07K16/28C12N5/0636C12N5/0638A61K2039/505A61K2039/545C07K2317/622C07K2317/73C07K2319/02C07K2319/03C07K2319/035C07K2319/30C07K2319/33
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Quick Facts
Patent No.
US 12,303,551
App. No.
17/040,472
Granted
May 20, 2025
Kind
B2
Abstract

The present disclosure relates to cellular immunotherapy compositions comprising a combination of immune cells or cellular subsets modified with chimeric engulfment receptors and chimeric antigen receptors/or T cell receptor binding proteins, and methods of using such cellular immunotherapy compositions.

Claims (46)

1. A combination cellular immunotherapy composition comprising:

(a) a first composition comprising a CD4+ T cell comprising a chimeric engulfment receptor (CER) comprising:

an extracellular domain comprising a Tim4 extracellular domain that binds to phosphatidylserine,

an engulfment signaling domain, wherein the engulfment signaling domain comprises a TLR signaling domain, a TRAF2 signaling domain, a TRAF6 signaling domain, a DAP12 signaling domain, a NFAM1 signaling domain, a Baff-R signaling domain, or a CD79b signaling domain, and

a transmembrane domain positioned between and connecting the extracellular domain and the engulfment signaling domain; and

(b) a second composition comprising a CD8+ T cell comprising:

(i) a chimeric antigen receptor (CAR) comprising:

an extracellular domain comprising an antibody binding domain that binds to a target antigen,

an intracellular signaling domain, and

a transmembrane domain positioned between and connecting the extracellular domain and the intracellular signaling domain; or

(ii) a recombinant T cell receptor (TCR) that binds to a target antigen.

2. The combination cellular immunotherapy composition of claim 1 , wherein:

(a) the CAR antibody binding domain comprises a scFv; and/or

(b) the CAR extracellular domain further comprises a spacer domain between the antibody binding domain and the transmembrane domain.

3. The combination cellular immunotherapy composition of claim 1 , wherein:

(a) the CAR transmembrane domain comprises a CD28, CD2, CD4, CD8, CD3ε, CD3δ, CD3ζ, CD25, CD27, CD40, CD79A, CD79B, CD80, CD86, CD95 (Fas), CD134 (OX40), CD137 (4-1BB), CD150 (SLAMF1), CD152 (CTLA4), CD200R, CD223 (LAG3), CD270 (HVEM), CD272 (BTLA), CD273 (PD-L2), CD274 (PD-L1), CD278 (ICOS), CD279 (PD-1), CD300, CD357 (GITR), A2aR, DAP10, FcRα, FcRβ, FcRγ, Fyn, GAL9, KIR, Lck, LAT, LRP, NKG2D, NOTCH1, NOTCH2, NOTCH3, NOTCH4, PTCH2, ROR2, Ryk, Slp76, SIRPα, pTα, TCRα, TCRβ, TIM3, TRIM, LPA5, or Zap70 transmembrane domain;

(b) the CAR intracellular signaling domain comprises an ITAM-containing activating signaling domain selected from CD3ζ, CD3γ, CD3δ, CD3ε, CD5, CD22, CD79a, CD278 (ICOS), DAP10, DAP12, and CD66d signaling domain;

(c) the CAR intracellular signaling domain comprises a first costimulatory signaling domain selected from CD27, CD28, 4-1BB, OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, and B7-H3 signaling domain;

or any combination of (a)-(c).

4. The combination cellular immunotherapy composition of claim 3 , wherein the CAR intracellular signaling domain comprises a second costimulatory signaling domain selected from CD27, CD28, 4-1BB, OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, and B7-H3 signaling domain.

5. The combination cellular immunotherapy composition of claim 1 , wherein the CAR is a first generation CAR, second generation CAR, third generation CAR, or TCR-CAR.

6. The combination cellular immunotherapy composition of claim 1 , wherein the target antigen of the CAR is a tumor antigen.

7. The combination cellular immunotherapy composition of claim 6 , wherein the target antigen of the CAR is a tumor antigen selected from the group consisting of CD138, CD38, CD33, CD123, CD72, CD79a, CD79b, mesothelin, PSMA, BCMA, ROR1, MUC-16, L1CAM, CD22, CD19, CD20, CD23, CD24, CD37, CD30, CA125, CD56, c-Met, EGFR, GD-3, HPV E6, HPV E7, MUC-1, HER2, folate receptor α, CD97, CD171, CD179a, CD44v6, WT1, VEGF-α, VEGFR1, IL-13Rα1, IL-13Rα2, IL-11Rα, PSA, FcRH5, NKG2D ligand, NY-ESO-1, TAG-72, CEA, ephrin A2, ephrin B2, Lewis A antigen, Lewis Y antigen, MAGE, MAGE-A1, RAGE-1, folate receptor β, EGFRviii, VEGFR-2, LGR5, SSX2, AKAP-4, FLT3, fucosyl GM1, GM3, o-acetyl-GD2, and GD2.

8. The combination cellular immunotherapy composition of claim 1 , wherein the recombinant TCR is an αβTCR, γδTCR, enhanced affinity TCR, soluble TCR, or single chain TCR.

9. The combination cellular immunotherapy composition of claim 1 , wherein the target antigen of the recombinant TCR is WT-1, mesothelin, MART-1, NY-ESO-1, MAGE-A3, HPV E7, survivin, a Fetoprotein, or a tumor neoantigen.

10. The combination cellular immunotherapy composition of claim 1 , wherein:

(a) the CER extracellular domain further comprises a spacer domain between the Tim4 extracellular domain and the transmembrane domain.

11. The combination cellular immunotherapy composition of claim 1 , wherein:

the CER transmembrane domain comprises a Tim1, Tim4, Tim3, FcR, CD8, CD28, MERTK, Axl, Tyro3, BAI1, CD4, DAP12, MRC1, FcR, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, or TLR9 transmembrane domain.

12. The combination cellular immunotherapy composition of claim 1 , wherein the CER engulfment signaling domain comprises a primary engulfment signaling domain and a secondary engulfment signaling domain.

13. The combination cellular immunotherapy composition of claim 12 , wherein the CER primary engulfment signaling domain and secondary engulfment signaling domain are each independently selected from MERTK, Tyro3, ItgB5, MRC1, ELMO, Axl, Syk, MyD88, FcγR1, FcγR2A, FcγR2B2, FcγR2C, FcγR3A, FcεR1, FcαR1, BAFF-R, DAP12, NFAM1, CD79b, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, Traf6, Traf2, and Traf3 signaling domain.

14. The combination cellular immunotherapy composition of claim 1 , wherein the CER comprises the amino acid sequence of any one of SEQ ID NOS: 94, 102 103, 105, 106, 112, 113, 95, 114, 96, 115, 116, 117, 97, 118, 98, 119, 99, 120, 121, 122, 123, 124, 125, 126, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 173, 156, 157, 163, 164, 165, 166, 167, 169, 170, 171, 172, 174, 175, 176, 177, 178, 179, 180, and 181.

15. The combination cellular immunotherapy composition of claim 1 , wherein:

(a) the CD4+ T cell is a naïve CD4+ T cell, an effector memory CD4+ T cell, or a central memory CD4+ T cell; and/or

(b) the CD8+ T cell is a naïve CD8+ T cell, an effector memory CD8+ T cell, or a central memory CD8+ T cell.

16. The combination cellular immunotherapy composition of claim 1 , wherein the CD4+ T cell, CD8+ T cell, or both are human.

17. The combination cellular immunotherapy composition of claim 1 , wherein the ratio of CD4+ T cells to CD8+ T cells in the composition is about 1:1, 1:2, 1:4, 1:8, 1:10, or 1:20.

18. The combination cellular immunotherapy composition of claim 1 , wherein the first composition and second composition each further comprises a pharmaceutically acceptable carrier.

19. The combination cellular immunotherapy composition of claim 1 , wherein the Tim4 extracellular domain comprises SEQ ID NO:90 or amino acids 25-314 of SEQ ID NO:90.

20. The combination cellular immunotherapy composition of claim 1 , wherein the TLR signaling domain comprises a TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, or TLR9 signaling domain.

21. A method of treating a subject having cancer comprising administering an effective amount of a combination cellular immunotherapy composition of claim 1 to the subject.

22. The method of claim 21 , wherein the cancer is a solid tumor, melanoma, non-small cell lung cancer, renal cell carcinoma, renal cancer, a hematological cancer, prostate cancer, castration-resistant prostate cancer, colon cancer, rectal cancer, gastric cancer, esophageal cancer, bladder cancer, head and neck cancer, thyroid cancer, breast cancer, triple-negative breast cancer, ovarian cancer, cervical cancer, lung cancer, urothelial cancer, pancreatic cancer, glioblastoma, hepatocellular cancer, myeloma, multiple myeloma, leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, myelodysplastic syndrome, brain cancer, CNS cancer, or malignant glioma.

23. The method of claim 21 , wherein the CD4+ T cell is autologous or allogeneic to the subject, the CD8+ T cell is autologous or allogeneic to the subject, or both.

24. The method of claim 21 , wherein the combination cellular immunotherapy composition is administered in combination with an additional therapeutic agent.

25. The method of claim 24 , wherein the additional therapeutic agent is an antibody, radiation therapy, chemotherapeutic agent, immune checkpoint molecule inhibitor therapy, small molecule therapy, cellular immunotherapy, oncolytic virus, electropulse therapy, UV light therapy high intensity focused ultrasound therapy, oncolytic virus, peptide, hormone, aptamer, anti-inflammatory agent, antibiotic, anti-fungal agent, or anti-viral agent.

26. The method of claim 21 , wherein the first composition and second composition are administered concurrently or sequentially to the subject.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 20, 2024
From: CERO THERAPEUTICS, INC.
To: CERO THERAPEUTICS HOLDINGS, INC.
Reel/Frame 069436/0937 →
Continuity (4)
Provisional Application 62734863 · Sep 21, 2018
Provisional Application 62652838 · Apr 4, 2018
Provisional Application 62649541 · Mar 28, 2018
Related Publication 20210023135A1 · Jan 28, 2021
References Cited (248)
US 5019368A · Epstein et al. · 1991 [cited by applicant]
US 5283173A · Fields et al. · 1994 [cited by applicant]
US 5468614A · Fields et al. · 1995 [cited by applicant]
US 5641863A · Schreiber et al. · 1997 [cited by applicant]
US 5641875A · Schreiber et al. · 1997 [cited by applicant]
US 5747498A · Schnur et al. · 1998 [cited by applicant]
US 5776910A · Schreiber et al. · 1998 [cited by applicant]
US 5821071A · Schreiber et al. · 1998 [cited by applicant]
US 6068983A · Schreiber et al. · 2000 [cited by applicant]
US 6475997B1 · Schreiber et al. · 2002 [cited by applicant]
US 6630313B2 · Fadok et al. · 2003 [cited by applicant]
US 7195761B2 · Holtzman et al. · 2007 [cited by applicant]
US 7247303B2 · Thorpe et al. · 2007 [cited by applicant]
US 7892544B2 · Pfeifer et al. · 2011 [cited by applicant]
US 7910333B2 · Chilcote et al. · 2011 [cited by applicant]
US 8025878B2 · Gellerfors et al. · 2011 [cited by applicant]
US 8119772B2 · Yang et al. · 2012 [cited by applicant]
US 8496938B2 · Smith et al. · 2013 [cited by applicant]
US 8940276B2 · Weihofen et al. · 2015 [cited by applicant]
US 8956616B2 · Thorpe et al. · 2015 [cited by applicant]
US 10093717B2 · Li et al. · 2018 [cited by applicant]
US 10125193B2 · Cooper · 2018 [cited by examiner]
US 10793641B2 · Wang et al. · 2020 [cited by applicant]
US 10980836B1 · Getts et al. · 2021 [cited by applicant]
US 11655282B2 · Corey et al. · 2023 [cited by applicant]
US 11708423B2 · Corey et al. · 2023 [cited by applicant]
US 20030072743A1 · Albert et al. · 2003 [cited by applicant]
US 20030095962A1 · Ueda et al. · 2003 [cited by applicant]
US 20030124114A1 · McIntire et al. · 2003 [cited by applicant]
US 20030130218A1 · Schreiber et al. · 2003 [cited by applicant]
US 20060002940A1 · Stevenson · 2006 [cited by applicant]
US 20060257359A1 · Francois et al. · 2006 [cited by applicant]
US 20070258897A1 · Devitt et al. · 2007 [cited by applicant]
US 20080213216A1 · Schreiber et al. · 2008 [cited by applicant]
US 20110165649A1 · Tyler et al. · 2011 [cited by applicant]
US 20130071414A1 · Dotti et al. · 2013 [cited by applicant]
US 20140162290A1 · Watanabe et al. · 2014 [cited by applicant]
US 20150023986A1 · Jones et al. · 2015 [cited by applicant]
US 20170058024A1 · West et al. · 2017 [cited by applicant]
US 20170151281A1 · Wagner et al. · 2017 [cited by applicant]
US 20170166622A1 · Baeuerle et al. · 2017 [cited by applicant]
US 20170166657A1 · O'Neill et al. · 2017 [cited by applicant]
US 20170209492A1 · June et al. · 2017 [cited by applicant]
US 20180186855A1 · Rosenthal · 2018 [cited by applicant]
US 20180186878A1 · Rosenthal · 2018 [cited by applicant]
US 20180244748A1 · Gill et al. · 2018 [cited by applicant]
US 20180291089A1 · Epstein et al. · 2018 [cited by applicant]
US 20180319862A1 · Thompson et al. · 2018 [cited by applicant]
US 20180334653A1 · O'Neill · 2018 [cited by applicant]
US 20190350972A1 · Mason et al. · 2019 [cited by applicant]
US 20200002402A1 · Emtage et al. · 2020 [cited by applicant]
US 20200055917A1 · Corey · 2020 [cited by applicant]
US 20200239592A1 · Vale et al. · 2020 [cited by applicant]
US 20200308305A1 · Corey · 2020 [cited by applicant]
US 20210015865A1 · Corey · 2021 [cited by applicant]
US 20210023135A1 · Corey · 2021 [cited by applicant]
US 20210024607A1 · Corey et al. · 2021 [cited by applicant]
US 20210087251A1 · Corey · 2021 [cited by applicant]
US 20210253696A1 · Corey et al. · 2021 [cited by applicant]
US 20220098273A1 · Corey · 2022 [cited by applicant]
EP 0566226B1 · 1995 [cited by applicant]
EP 0520722B1 · 1996 [cited by applicant]
EP 0787722A1 · 1997 [cited by applicant]
EP 0837063A1 · 1998 [cited by applicant]
EP 0564409B1 · 2000 [cited by applicant]
WO WO9633980A1 · 1996 [cited by applicant]
WO WO9702266A1 · 1997 [cited by applicant]
WO WO9709433A1 · 1997 [cited by applicant]
WO WO9730034A1 · 1997 [cited by applicant]
WO WO9738983A1 · 1997 [cited by applicant]
WO WO9749688A1 · 1997 [cited by applicant]
WO WO9810767A2 · 1998 [cited by applicant]
WO WO9903854A1 · 1999 [cited by applicant]
WO WO0168709A1 · 2001 [cited by applicant]
WO WO0185207A2 · 2001 [cited by applicant]
WO WO02066470A1 · 2002 [cited by applicant]
WO WO03064383A2 · 2003 [cited by applicant]
WO WO2004067569A1 · 2004 [cited by applicant]
WO WO2005019429A2 · 2005 [cited by applicant]
WO WO2005090573A2 · 2005 [cited by applicant]
WO WO2005097211A2 · 2005 [cited by applicant]
WO WO2006122806A2 · 2006 [cited by applicant]
WO WO2007084786A1 · 2007 [cited by applicant]
WO WO2009036082A2 · 2009 [cited by applicant]
WO WO2009055730A1 · 2009 [cited by applicant]
WO WO2013074916A1 · 2013 [cited by applicant]
WO WO2013192294A1 · 2013 [cited by applicant]
WO WO2014031687A1 · 2014 [cited by applicant]
WO WO2014059173A2 · 2014 [cited by applicant]
WO WO2014153114A1 · 2014 [cited by applicant]
WO WO2015066262A1 · 2015 [cited by applicant]
WO WO2015123642A1 · 2015 [cited by applicant]
WO WO2015184228A1 · 2015 [cited by applicant]
WO WO2016019300A1 · 2016 [cited by applicant]
WO WO2016044605A1 · 2016 [cited by applicant]
WO WO2016126608A1 · 2016 [cited by applicant]
WO WO2017019848A1 · 2017 [cited by applicant]
WO WO2017025944A2 · 2017 [cited by applicant]
WO WO2017083700A1 · 2017 [cited by applicant]
WO WO2017205747A1 · 2017 [cited by applicant]
WO WO2017219916A1 · 2017 [cited by applicant]
WO WO2018031419A1 · 2018 [cited by applicant]
WO WO2018064076A1 · 2018 [cited by applicant]
WO WO2018132695A1 · 2018 [cited by applicant]
WO WO2018212770A1 · 2018 [cited by applicant]
WO WO2018220224A1 · 2018 [cited by applicant]
WO WO2019067328A1 · 2019 [cited by applicant]
WO WO2019079529A1 · 2019 [cited by applicant]
WO WO2019086512A1 · 2019 [cited by applicant]
WO WO2019091478A1 · 2019 [cited by applicant]
WO WO2019157440A1 · 2019 [cited by applicant]
WO WO2019191332A1 · 2019 [cited by applicant]
WO WO2019191334A1 · 2019 [cited by applicant]
WO WO2019191339A1 · 2019 [cited by applicant]
WO WO2019191340A1 · 2019 [cited by applicant]
WO WO2020114518A1 · 2020 [cited by applicant]
WO WO2020223550A1 · 2020 [cited by applicant]
WO WO2021003428A1 · 2021 [cited by applicant]
WO WO2021067875A1 · 2021 [cited by applicant]
WO WO2022036265A1 · 2022 [cited by applicant]
WO WO2022036285A1 · 2022 [cited by applicant]
WO WO2022036287A1 · 2022 [cited by applicant]
WO WO2023010097A1 · 2023 [cited by applicant]
Wong K et al. Phosphatidylserine receptor Tim-4 is essential for the maintenance of the homeostatic state of resident peritoneal macrophages. Proc Natl Acad Sci U S A. May 11, 2010; 107(19):8712-7. doi: 10.1073/pnas.091… [cited by examiner]
Moller-Tank S, Maury W. Phosphatidylserine receptors: enhancers of enveloped virus entry and infection. Virology. Nov. 2014;468-470:565-580. doi: 10.1016/j.virol.2014.09.009. Epub Sep. 29, 2014. PMID: 25277499; PMCID: P… [cited by examiner]
Segawa K, Nagata S. An Apoptotic ‘Eat Me’ Signal: Phosphatidylserine Exposure. Trends Cell Biol. Nov. 2015;25(11):639-650. doi: 10.1016/j.tcb.2015.08.003. Epub Oct. 1, 2015. PMID: 26437594. (Year: 2015). [cited by examiner]
Morrissey MA, Williamson AP, Steinbach AM, Roberts EW, Kern N, Headley MB, Vale RD. Chimeric antigen receptors that trigger phagocytosis. Elife. Jun. 4, 2018;7:e36688. doi: 10.7554/eLife.36688. PMID: 29862966; PMCID: PM… [cited by examiner]
Corey D, Haeseleer F, Hou J, Corey L. Novel engineered chimeric engulfment receptors trigger T cell effector functions against SIV-infected CD4+ T cells. Mol Ther Methods Clin Dev. Nov. 15, 2022;28:1-10. doi: 10.1016/j.… [cited by examiner]
Sommermeyer D. Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo. Leukemia. Feb. 2016;30(2):492-500. doi: 10.1038/leu.2015.247. Epub Sep. … [cited by examiner]
Blackburn et al., “Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection,” [cited by applicant]
Aderem, “Phagocytosis and the Inflammatory Response,” [cited by applicant]
Agaugue et al., “224. Development of Safer & Optimized CAR-T Cells Using Lentiviral Vectors,” [cited by applicant]
Aggen et al., “Single-chain V(alpha)V(beta) T-cell receptors function without mispairing with endogenous TCR chains,” [cited by applicant]
Albert et al., “αvβ5 integrin recruits the CrkII-Dock180-Rac1 complex for phagocytosis of apoptotic cells,” [cited by applicant]
Alder et al., “Antibody responses of variable lymphocyte receptors in the lamprey,” [cited by applicant]
Altman et al., “Phenotypic Analysis of Antigen-Specific T Lymphocytes,” [cited by applicant]
Arandjelovic et al., “Phagocytosis of apoptotic cells in homeostasis,” [cited by applicant]
Baral et al., “Experimental therapy of African trypanosomiasis with a nanobody-conjugated human trypanolytic factor,” [cited by applicant]
Barthelemy et al., “Comprehensive Analysis of the Factors Contributing to the Stability and Solubility of Autonomous Human VH Domains*,” [cited by applicant]
Belzile et al., “Antibody targeting of phosphatidylserine for the detection and immunotherapy of cancer,” [cited by applicant]
Castellano et al., “Membrane recruitment of Rac1 triggers phagocytosis,” [cited by applicant]
Clackson et al., “Making antibody fragments using phage display libraries,” [cited by applicant]
Cortez-Retamozo et al., “Efficient Cancer Therapy with a Nanobody-Based Conjugate,” [cited by applicant]
Dillon et al., “Annexin V Binds to Viable B Cells and Colocalizes with a Marker of Lipid Rafts upon B Cell Receptor Activation,” [cited by applicant]
Duclos et al., “Rab5 regulates the kiss and run fusion between phagosomes and endosomes and the acquisition of phagosome leishmanicidal properties in RAW 264.7 macrophages,” [cited by applicant]
Engels et al., “Retroviral Vectors for High-Level Transgene Expression in T Lymphocytes,” [cited by applicant]
Feng et al., “Interleukin-6 increases prostate cancer cells resistance to bicalutamide via TIF2,” [cited by applicant]
Fesnak et al., “Engineered T Cells: The Promise and Challenges of Cancer Immunotherapy,” [cited by applicant]
Frecha et al., “Advances in the Field of Lentivector-based Transduction of T and B Lymphocytes for Gene Therapy,” [cited by applicant]
Gerber et al., “Tumor-specific targeting by Bavituximab, a phosphatidylserine-targeting monoclonal antibody with vascular targeting and immune modulating properties, in lung cancer xenografts,” [cited by applicant]
Ghahroudi et al., “Selection and identification of single domain antibody fragments from camel heavy-chain antibodies,” [cited by applicant]
Green et al., “Mitochondria and Apoptosis,” [cited by applicant]
Greenberg et al., “Clustered syk tyrosine kinase domains trigger phagocytosis,” [cited by applicant]
Greenberg, “Programmed cell death: A way of life for plants,” [cited by applicant]
Guest et al., “The Role of Extracellular Spacer Regions in the Optimal Design of Chimeric Immune Receptors: Evaluation of Four Different scFvs and Antigens,” [cited by applicant]
Hamers-Casterman et al., “Naturally occurring antibodies devoid of light chains,” [cited by applicant]
Hanayama et al., “Identification of a factor that links apoptotic cells to phagocytes,” [cited by applicant]
Hartt Meyers et al., “TIM-4 is the ligand for TIM-1, and the TIM-1—TIM-4 interaction regulates T cell proliferation,” [cited by applicant]
Herrin et al., “Structure and specificity of lamprey monoclonal antibodies,” [cited by applicant]
Hochreiter-Hufford et al., “Clearing the Dead: Apoptotic Cell Sensing, Recognition, Engulfment, and Digestion,” [cited by applicant]
Hudecek et al., “Receptor Affinity and Extracellular Domain Modifications Affect Tumor Recognition by ROR1-Specific Chimeric Antigen Receptor T Cells,” [cited by applicant]
Hudecek et al., “The Nonsignaling Extracellular Spacer Domain of Chimeric Antigen Receptors Is Decisive for In Vivo Antitumor Activity,” [cited by applicant]
Hull et al., “The Mononuclear Phagocyte System in Homeostasis and Disease: A Role for Heme Oxygenase-1,” [cited by applicant]
International Search Report and Written Opinion, mailed Aug. 19, 2019, for International Application No. PCT/US2019/024441, 13 pages. [cited by applicant]
International Search Report and Written Opinion, mailed Feb. 6, 2018, for International Application No. PCT/US17/53553, 13 pages. [cited by applicant]
International Search Report and Written Opinion, mailed Jun. 28, 2019, for International Application No. PCT/US2019/024442, 12 pages. [cited by applicant]
International Search Report and Written Opinion, mailed Jun. 7, 2019, for International Application No. PCT/US2019/024433, 13 pages. [cited by applicant]
International Search Report and Written Opinion, mailed Mar. 25, 2019, for International Application No. PCT/US2018/052297, 10 pages. [cited by applicant]
International Search Report and Written Opinion, mailed May 29, 2019, for International Application No. PCT/US2019/024435, 12 pages. [cited by applicant]
Jespers et al., “Aggregation-resistant domain antibodies selected on phage by heat denaturation,” [cited by applicant]
Jolly, “9: Emerging Viral Vectors,” [cited by applicant]
June, “Adoptive T cell therapy for cancer in the clinic,” [cited by applicant]
Khogeer et al., “Antiphosphatidylserine antibodies as diagnostic indicators of antiphospholipid syndrome,” [cited by applicant]
Kitchen et al., “Engineering Antigen-Specific T Cells from Genetically Modified Human Hematopoietic Stem Cells in Immunodeficient Mice,” [cited by applicant]
Kochenderfer et al., “Construction and Pre-clinical Evaluation of an Anti-CD19 Chimeric Antigen Receptor,” [cited by applicant]
Krisky et al., “Development of herpes simplex virus replication-defective multigene vectors for combination gene therapy applications,” [cited by applicant]
Kruskal et al., “Phagocytic Chimeric Receptors Require Both Transmembrane and Cytoplasmic Domains from the Mannose Receptor,” [cited by applicant]
Luo et al., “Development of genetically engineered CD4 [cited by applicant]
Miksa et al., “A novel method to determine the engulfment of apoptotic cells by macrophages using pHrodo succinimidyl ester,” [cited by applicant]
Misyurin, “Structure and Functions of Main Apoptosis Receptors and Ligands,” Russian Journal of Biotherapy 14(2):23-30, 2015. [cited by applicant]
Miyanishi et al., “Identification of Tim4 as a phosphatidylserine receptor,” [cited by applicant]
Morgan et al., “Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes,” [cited by applicant]
Morrissey et al., “Chimeric antigen receptors that trigger phagocytosis,” eLife, 2018. (21 pages). [cited by applicant]
Nguyen et al., “Heavy-chain antibodies in [cited by applicant]
Nguyen et al., “The Specific Variable Domain of Camel Heavy-chain Antibodies is Encoded in the Germline,” [cited by applicant]
Nishi et al., “Systematic characterization of deubiquitylating enzymes for roles in maintaining genome integrity,” [cited by applicant]
Nishi et al., “Tim4- and MerTK-Mediated Engulfment of Apoptotic Cells by Mouse Resident Peritoneal Macrophages,” [cited by applicant]
Penberthy et al., “Apoptotic cell recognition receptors and scavenger receptors,” [cited by applicant]
Pfeifer et al., “Gene Therapy: Promises and Problems,” [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”,” [cited by applicant]
Ravichandran “Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums,” [cited by applicant]
Rossi et al., “Genetic therapies against HIV,” [cited by applicant]
Roux et al., “Structural analysis of the nurse shark (new) antigen receptor (NAR): Molecular convergence of NAR and unusual mammalian immunoglobulins,” [cited by applicant]
Sandberg et al., “Human T-cell lines with well-defined T-cell receptor gene rearrangements as controls for the BIOMED-2 multiplex polymerase chain reaction tubes,” [cited by applicant]
Sato et al., “Enhancement of Fcy Receptor-Mediated Phagocytosis by Transforming Mutants of Cbl1,” [cited by applicant]
Scatchard et al., “The Attractions of Proteins for Small Molecules and Ions,” [cited by applicant]
Schmitt et al., “T Cell Receptor Gene Therapy for Cancer,” [cited by applicant]
Scholten et al., “Codon modification of T cell receptors allows enhanced functional expression in transgenic human T cells,” [cited by applicant]
Schutters et al., “Phosphatidylserine targeting for diagnosis and treatment of human diseases,” [cited by applicant]
Stone et al., “A novel T cell receptor single-chain signaling complex mediates antigen-specific T cell activity and tumor control,” [cited by applicant]
Verhoeyen et al., “Chapter 8: Lentiviral Vector Gene Transfer into Human T Cells,” [cited by applicant]
Vincke et al., “General Strategy to Humanize a Camelid Single-domain Antibody and Identification of a Universal Humanized Nanobody Scaffold,” [cited by applicant]
Wälchli et al., “A Practical Approach to T-Cell Receptor Cloning and Expression,” [cited by applicant]
Walseng et al., “A TCR-based Chimeric Antigen Receptor,” [cited by applicant]
Wang et al., “A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells,” [cited by applicant]
Williamson et al., “Cellular reconstitution of apoptotic cell clearance reveals a multi-step phosphorylation mechanism for Draper receptor triggering,” [cited by applicant]
Williamson et al., “Abstract A165: Engineering approaches to uncover the mechanism of apoptotic cell clearance by a conserved signaling system,” [cited by applicant]
Williamson et al., “Abstract PR15: Engineering phagocytic signaling,” CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival, New York, New York, Sep. 25-28, 2016. (4 pages). [cited by applicant]
Williamson et al., “Spatial control of Draper receptor signaling initiates apoptotic cell engulfment,” [cited by applicant]
Wilson, “Analyzing Biomolecular Interactions,” [cited by applicant]
Wolff et al., “Monoclonal Antibody Homodimers: Enhanced Antitumor Activity in Nude Mice,” [cited by applicant]
Zhang et al., “Transduction of Human T Cells with a Novel T-Cell Receptor Confers Anti-HCV Reactivity,” [cited by applicant]
Zhao et al., “Primary Human Lymphocytes Transduced with NY-ESO-1 Antigen-Specific TCR Genes Recognize and Kill Diverse Human Tumor Cell Lines,” [cited by applicant]
Zaritskaya et al., “New flow cytometric assays for monitoring cell-mediated cytotoxicity,” [cited by applicant]
Burns et al., “A high molecular weight-melanoma associated antigen-specific chimeric antigen receptor redirects lymphocytes to target human melanomas,” [cited by applicant]
Chen et al., “Fusion Protein Linkers: Property, Design and Functionality,” [cited by applicant]
Colman, “Effects of amino acid sequence changes on antibody-antigen interactions,” [cited by applicant]
Cordoba et al., “The large ectodomains of CD45 and CD148 regulate their segregation from and inhibition of ligated T-cell receptor,” [cited by applicant]
Dolezal et al., “ScFv multimers of the anti-neuraminidase antibody NC10: shortening of the linker in single-chain Fv fragment assembled in V(L) to V(H) orientation drives the formation of dimers, trimers, tetramers and … [cited by applicant]
Jones et al., “Lentiviral Vector Design for Optimal T Cell Receptor Gene Expression in the Transduction of Peripheral Blood Lymphocytes and Tumor-Infiltrating Lymphocytes,” [cited by applicant]
Maeda et al., “Engineering of Functional Chimeric Protein [cited by applicant]
Muller et al., “Spliceosomal Peptide P140 for Immunotherapy of Systemic Lupus Erythematosus: Results of an Early Phase II Clinical Trial,” [cited by applicant]
Safdari et al., “Antibody humanization methods—a review and update,” [cited by applicant]
Srivastava et al., “Engineering CAR-T Cells: Design Concepts,” [cited by applicant]
Teplyakov et al., “Antibody modeling assessment II. Structures and models,” [cited by applicant]
Vallabhapurapu et al., “Variation in human cancer cell external phosphatidylserine is regulated by flippase activity and intracellular calcium,” [cited by applicant]
Delgado Tascón et al., “The granulocyte orphan receptor CEACAM4 is able to trigger phagocytosis of bacteria,” [cited by applicant]
Kobayashi et al., “TIM-1 and TIM-4 Glycoproteins Bind Phosphatidylserine and Mediate Uptake of Apoptotic Cells,” [cited by applicant]
Nakaya, “Research on Molecular Mechanisms of Engulfment of Apoptotic Cells”, [cited by applicant]
Moller-Tank et al., “Characterizing Functional Domains for TIM-Mediated Enveloped Virus Entry”, J. Virology, Jun. 2014, 88(12): 6702-6713). [cited by applicant]
Nix, et al., “In Vitro-Selected Nanobody-Based Cellular Therapy Targeting CD72 for Treatement of Refractory B-Cell Malignancies”, Blood, American Society of Hematology, vol. 134, Nov. 2019, 4 pages. [cited by applicant]
Parmar et al., “The CHK1 Inhibitor Prexasertib Exhibits Monotherapy Activity in High-Grade Serous Ovarian Cancer Models and Sensitizes to PARP Inhibition”, Translational Cancer Mechanisms and Therapy, Clinical Cancer Re… [cited by applicant]
Takeshi, et al., “Regulation of Immunity by Toll-like Receptor Functions: TheirPhysiological and Pathological Roles,” Journal of Gifu Dental Society, 2011?vol. 37?pp. 138-158. [cited by applicant]
Qin, et al. “Prelinical Development of Bivalent Chimeric Antigen Receptors Targeting Both CD19 and CD22,” Molecular Therapy: Oncolytics, vol. 11, Dec. 2018, pp. 127-137. [cited by applicant]
Ortiz, et al. “The evolutionary history of the CD209 (DC-Sign) family in humans and non-human primates,” Genes and Immunity, Jun. 2008, 2008(9), pp. 483-492. [cited by applicant]
Hayashi et al., “The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5,” Nature, 410(6832), Apr. 2001, pp. 1099-1103. [cited by applicant]
Chen et al., “TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis,” [cited by applicant]
Park et al., “The Phosphatidylserine Receptor TIM-4 Does Not Mediate Direct Signaling,” [cited by applicant]
Blasius et al., “Intracellular Toll-like Receptors,” [cited by applicant]
Kao et al., “Systematic Comparison of the EF-1 Alpha Short (EFS) and Viral Promoters for Gene Modification of Human Primary Cells for Clinical Applications,” [cited by applicant]
Yang et al., “Development of optimal bicistronic lentiviral vectors facilitates high-level TCR gene expression and robust tumor cell recognition,” [cited by applicant]
U.S. Appl. No. 18/322,450, filed May 23, 2023. [cited by applicant]
U.S. Appl. No. 18/527,075, filed Dec. 1, 2023. [cited by applicant]
Moller-Tank S et al. Phosphatidylserine receptors: enhancers of enveloped virus entry and infection. Virology. Nov. 2014;468-470:565-580. doi: 10.1016/j.virol.2014.09.009. Epub Sep. 29, 2014. PMID: 25277499; PMCID: PMC4… [cited by applicant]
Segawa K et al. An Apoptotic ‘Eat Me’ Signal: Phosphatidylserine Exposure. Trends Cell Biol. Nov. 2015;25 (11):639-650. doi: 10.1016/j.tcb.2015.08.003. Epub Oct. 1, 2015. PM ID: 26437594. (Year: 2015). [cited by applicant]
Sommermeyer D. Chimeric antigen receptor-modified T cells derived from defined CDS+ and CD4+ subsets confer superior antitumor reactivity in vivo. Leukemia. Feb. 2016;30(2):492-500. doi: 10.1038/leu.2015.247. Epub Sep. … [cited by applicant]
Genbank Accession No. NP _612388 (2006) (Year: 2006). [cited by applicant]
Genbank Accession No. NP _848874 (2009) (Year: 2009). [cited by applicant]