IP Library › Granted Patent US 12,404,315
Granted Patent B2
US 12,404,315 · App. 17/557,654 · Granted Sep 2, 2025

Protease-activating CD45-gate CAR

Inventors: Shanshan Lang (San Mateo, CA); Thomas John Van Blarcom (Oakland, CA); Michael Thomas Bethune (Castro Valley, CA); Siler Panowski (Berkeley, CA); Nguyen Tan (Berkeley, CA); Yi Zhang (Foster City, CA); Barbra Johnson Sasu (San Francisco, CA); Zhe Li (Burlingame, CA)
Assignees: Allogene Therapeutics, Inc.; Pfizer Inc.
C07K14/7051A61K40/11A61K40/15A61K40/31A61K40/4224A61K40/4252A61K40/4257C07K14/70521C07K14/70596C07K16/28C07K16/289C07K19/00C12N5/0634C12N5/0636C12N5/10C12N15/79A61K2239/31A61K2239/38A61K2239/49A61K2239/55A61K2239/59C07K2317/22C07K2317/24C07K2317/31C07K2317/569C07K2319/01C07K2319/31C07K2319/50
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,404,315
App. No.
17/557,654
Granted
Sep 2, 2025
Kind
B2
Abstract

A reversibly gated effector polypeptide e.g. a chimeric antigen receptor (protease-activating CD45-gate CAR) comprising an extracellular CD45 recruiting domain, a protease-cleavable linker, and a polypeptide comprising an extracellular ligand binding domain, a transmembrane domain, and an intracellular domain. Nucleic acids including vectors and expression vectors that encode the protease-activating CD45-gate CAR and cells including immune cells such as T cells that comprise and express the nucleic acids. Methods of treatment of various conditions including various forms of cancer comprising administering the cells including CAR T cell therapy. In some embodiments, the CD45 gate at least partially inhibits activation of the protease-activating CD45-gate CAR when the protease-activating CD45-gate CAR binds antigen. The inhibition is at least partially diminished, relieved and/or eliminated when the protease-activating CD45-gate CAR is exposed to a protease that can cleave the linker.

Claims (38)

1. A protease-activating CD45-gate chimeric antigen receptor (CD45-gate CAR) comprising an extracellular domain, a transmembrane domain, and an intracellular domain, wherein the extracellular domain comprises:

a CD45 recruiting domain comprising an anti-CD45 antibody, or an antigen binding fragment thereof,

an antigen binding domain, and

a linker comprising one or more protease cleavage sites that is cleavable by at least one protease.

2. The protease-activating CD45-gate CAR of claim 1 , wherein the intracellular domain comprises at least one signaling domain that is reversibly inactivated by CD45.

3. The protease-activating CD45-gate CAR of claim 1 , wherein the linker is between the CD45 recruiting domain and the antigen binding domain.

4. The protease-activating CD45-gate CAR of claim 1 , wherein the CD45 recruiting domain comprises one or more linkers.

5. The CD45-gate CAR of claim 1 , wherein the linker connects the carboxy terminus of the CD45 recruiting domain to the amino terminus of the antigen binding domain, and further wherein the intracellular domain comprises at least one signaling domain that is reversibly inactivated by CD45.

6. The protease-activating CD45-gate CAR of claim 1 , wherein the CD45 recruiting domain comprises one or more of an anti-CD45 antibody antigen binding fragment.

7. The protease-activating CD45-gate CAR of claim 6 , wherein the anti-CD45 antibody antigen binding fragment comprises an anti-CD45 scFv.

8. The protease-activating CD45-gate CAR of claim 1 , wherein the CD45 recruiting domain comprises the amino acid sequence of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6, without the signal sequence of SEQ ID NO:1.

9. The protease-activating CD45-gate CAR of claim 1 , wherein the antigen binding domain specifically binds BCMA, MUC16, EGFR, EGFRvIII, MUC1, Flt-3, WT-1, CD20, CD23, CD30, CD38, CD70, CD33, CD133, MHC-WT1, TSPAN10, MHC-PRAME, MHC-NY-ESO1, HER2, (Carbonic anhydrase IX, LIV1, ADAM10, CHRNA2, LeY, NKG2D, CS1, CD44v6, ROR1, CD19, Claudin-18.2.

10. The protease-activating CD45 gate CAR of claim 1 , wherein the linker comprising at least one protease cleavage site has a length of 15-100 amino acids.

11. The protease-activating CD45-gate CAR of claim 1 , wherein the linker comprises one or more protease cleavage sites that are cleavable by at least one protease which is present in a tumor microenvironment.

12. The protease-activating CD45-gate CAR of claim 1 , wherein the linker comprises at least one protease cleavage site that is cleavable by a serine protease, a cysteine-type lysosomal protease, a metalloproteinase, a coagulation factor protease, or an aspartyl-type lysosomal protease.

13. The protease-activating CD45-gate CAR of claim 1 , wherein the linker comprises at least one protease cleavage site that is cleavable by matrix metalloproteinase (MMP), matriptase (MT-SP1), trypsin, plasmin, prostate-specific antigen (PSA), urokinase plasminogen activator (uPA), urokinase plasminogen activator receptor (uPAR), legumain, a disintegrin and metalloproteinase (ADAM), a transmembrane Serine Protease (TMPRSS), Granzyme B, activated protein C, Caspase, Cathepsin, Chymase, Elastase, Guanidinobenzoatase, HtrA1, Human Neutrophil Elastase, Lactoferrin, Marapsin, NS3/4A, PACE4, tissue plasminogen activator (tPA), thrombin, DESC1, DPP-4, FAP, Hepsin, Matriptase-2, secretase, kallikrein-related peptidase (KLK), and tryptase.

14. The protease-activating CD45-gate CAR of claim 1 , wherein the linker comprises one or more protease cleavage sites, wherein the protease cleavage site comprises the amino acid sequence of SEQ ID NO: 32, 91-98, 103-105 or SEQ ID NO: 106.

15. The protease-activating CD45-gate CAR of claim 1 , wherein the linker comprises one or more amino acid sequences of SEQ ID NO: 53, 89, or 90.

16. The protease-activating CD45-gate CAR of claim 1 , wherein the linker comprises one or more amino acid sequences of SEQ ID NO: 8-10, 53, 89, 90, 99-102, 107-120, 172-176 or SEQ ID NO: 177.

17. The protease-activating CD45-gate CAR of claim 1 , wherein the linker comprises two or more protease cleavage sites and each cleavage site is the same as or different from any of the other cleavage sites.

18. The protease-activating CD45-gate CAR of claim 1 , wherein the intracellular domain comprises the cytoplasmic signaling domain of one or more of CD3 zeta, CD28, and CD2.

19. The protease-activating CD45-gate CAR of claim 1 , wherein the intracellular domain comprises at least one costimulatory domain.

20. The protease-activating CD45-gate CAR of claim 19 , wherein the at least one costimulatory domain is a signaling region of CD28, OX-40, 4-1BB/CD137, CD2, CD7, CD27, CD30, CD40, inducible T cell costimulator (ICOS), lymphocyte function-associated antigen-1 (LFA-1), CD3 gamma, CD3 delta, CD3 epsilon, CD247, CD276 (B7-H3), LIGHT (TNFSF14), NKG2C, Ig alpha (CD79a), DAP-10, Fc gamma receptor, MHC class I molecule, Signaling Lymphocytic Activation Molecules (SLAM proteins), BTLA, a Toll ligand receptor, ICAM-1, CDS, GITR, BAFFR, HVEM (LIGHTR), KIRDS2, NKp80 (KLRF1), NKp44, NKp30, NKp46, CD19, CD4, CD8alpha, CD8beta, IL-2R beta, IL-2R gamma, IL-7R alpha, ITGA4, VLA1, ITGA6, ITGAD, ITGAE, ITGAL, IT GAM, ITGAX, ITGB1, ITGB7, NKG2D, TNFR2, TRANCE/RANKL, DNAMI (CD226), CD84, CD96 (Tactile), CEACAM1, CRT AM, Ly9 (CD229), CD 160 (BY55), PSGL1, CD100 (SEMA4D), CD69, SELPLG (CD162), LTBR, LAT, GADS, SLP-76, PAG/Cbp, CD 19a, a ligand that specifically binds with CD83, or any combination thereof.

21. The protease-activating CD45-gate CAR of claim 1 , further comprising a signal sequence optionally wherein the signal sequence is a CD8 signal sequence comprising the amino acid sequence of SEQ ID NO: 1.

22. The protease-activating CD45-gate CAR of claim 1 , wherein the protease-activating CD45-gate CAR comprises the amino acid sequence of any one of SEQ ID NOs: 11, 16-31, 56, 75, 76, 77, 78, 79, and 121-170 or a variant thereof, wherein the variant does not comprise the amino acid sequence of the HA tag of SEQ ID NO: 2, does not comprise the amino acid sequence of the V5 peptide motif of SEQ ID NO: 55, or does not comprise the signal sequence of SEQ ID NO: 1.

23. A nucleic acid encoding the protease-activating CD45-gate CAR of claim 1 .

24. An engineered immune cell comprising the nucleic acid of claim 23 .

25. A vector comprising the nucleic acid of claim 23 .

26. The vector of claim 25 , wherein the vector is an expression vector.

27. An engineered immune cell comprising the vector of claim 25 .

28. An engineered immune cell comprising the protease-activating CD45-gate CAR of claim 1 .

29. The engineered immune cell of claim 28 , wherein the immune cell is a T cell, an NK cell, or a dendritic cell.

30. The engineered immune cell of claim 29 , wherein the T cell is a tumor infiltrating lymphocyte, an iPSC-derived T cell, a TCR-expressing cell, or an NK-T cell.

31. A population of cells comprising at least about 1×10 4 , 1×10 5 , 1×10 6 , 1×10 7 or 1×10 8 of the engineered immune cell of claim 28 .

32. A pharmaceutical composition comprising the engineered immune cell of claim 28 and a pharmaceutically acceptable carrier.

33. A method of treating cancer in a patient comprising administering to the patient the engineered immune cell of claim 28 , and wherein the cancer expresses an antigen that is recognized and bound by the antigen binding domain of the CD45-gate CAR.

34. The method of claim 33 , wherein the cancer is a solid tumor cancer or a liquid tumor cancer.

35. A method of treating a patient who has a tumor characterized by a protease-rich tumor microenvironment, comprising administering to the patient the engineered immune cell of claim 28 , and wherein the tumor expresses an antigen that is recognized and bound by the antigen binding domain of the CD45-gate CAR.

Continuity (3)
Provisional Application 63289984 · Dec 15, 2021
Provisional Application 63128667 · Dec 21, 2020
Related Publication 20220227832A1 · Jul 21, 2022
References Cited (163)
US 4683195A · Mullis et al. · 1987 [cited by applicant]
US 4683202A · Mullis · 1987 [cited by applicant]
US 4754065A · Levenson et al. · 1988 [cited by applicant]
US 4800159A · Mullis et al. · 1989 [cited by applicant]
US 5037743A · Welch et al. · 1991 [cited by applicant]
US 5143830A · Holland et al. · 1992 [cited by applicant]
US 5858358A · June et al. · 1999 [cited by applicant]
US 5883223A · Gray et al. · 1999 [cited by applicant]
US 6011138A · Reff et al. · 2000 [cited by applicant]
US 6106834A · Lazarovits et al. · 2000 [cited by applicant]
US 6352694B1 · June et al. · 2002 [cited by applicant]
US 6534055B1 · June et al. · 2003 [cited by applicant]
US 6692964B1 · June et al. · 2004 [cited by applicant]
US 6797514B2 · Brenson et al. · 2004 [cited by applicant]
US 6867041B2 · Berenson et al. · 2005 [cited by applicant]
US 6887466B2 · June et al. · 2005 [cited by applicant]
US 6905680B2 · June et al. · 2005 [cited by applicant]
US 6905681B1 · June et al. · 2005 [cited by applicant]
US 6905874B2 · Berenson et al. · 2005 [cited by applicant]
US 7067318B2 · June et al. · 2006 [cited by applicant]
US 7144575B2 · June et al. · 2006 [cited by applicant]
US 7172869B2 · June et al. · 2007 [cited by applicant]
US 7175843B2 · June et al. · 2007 [cited by applicant]
US 7232566B2 · June et al. · 2007 [cited by applicant]
US 7622119B2 · Sugiyama · 2009 [cited by applicant]
US 7709226B2 · Foote · 2010 [cited by applicant]
US 9169328B2 · Springgs et al. · 2015 [cited by applicant]
US 10808035B2 · Chmielewsk et al. · 2020 [cited by applicant]
US 10815301B2 · Kochenderfer et al. · 2020 [cited by applicant]
US 11077144B2 · Galetto et al. · 2021 [cited by applicant]
US 20060121005A1 · Berenson et al. · 2006 [cited by applicant]
US 20130165389A1 · Schellenberger et al. · 2013 [cited by applicant]
US 20160152725A1 · Cheung · 2016 [cited by applicant]
US 20170204139A1 · Moore et al. · 2017 [cited by applicant]
US 20180148503A1 · Scheinberg et al. · 2018 [cited by applicant]
US 20200231699A1 · Terrett et al. · 2020 [cited by applicant]
US 20200246383A1 · Lebeau et al. · 2020 [cited by applicant]
US 20210115102A1 · Winston et al. · 2021 [cited by applicant]
US 20210206848A1 · Garcia · 2021 [cited by examiner]
US 20210269501A1 · Powell et al. · 2021 [cited by applicant]
US 20210277141A1 · Zhao et al. · 2021 [cited by applicant]
US 20220023346A1 · Bethune et al. · 2022 [cited by applicant]
US 20230357424A1 · Lupardus · 2023 [cited by examiner]
CN 1568198A · 2005 [cited by applicant]
CN 109628492A · 2019 [cited by applicant]
CN 109680002A · 2019 [cited by applicant]
EP 1664122B1 · 2010 [cited by applicant]
WO 2002077029A2 · 2002 [cited by applicant]
WO 2005026210A2 · 2005 [cited by applicant]
WO 2013104804A2 · 2013 [cited by applicant]
WO 2013130683A2 · 2013 [cited by applicant]
WO 2016014565A2 · 2016 [cited by applicant]
WO 2016014576A1 · 2016 [cited by applicant]
WO 2016016341A1 · 2016 [cited by applicant]
WO 2016115559A1 · 2016 [cited by applicant]
WO 2016118629A1 · 2016 [cited by applicant]
WO 2016149368A1 · 2016 [cited by applicant]
WO 2016166630A1 · 2016 [cited by applicant]
WO 2017009473A1 · 2017 [cited by applicant]
WO 2017025038A1 · 2017 [cited by applicant]
WO 2017025323A1 · 2017 [cited by applicant]
WO 2017125830A1 · 2017 [cited by applicant]
WO 2017173410A1 · 2017 [cited by applicant]
WO 2018006882A1 · 2018 [cited by applicant]
WO 2018072025A1 · 2018 [cited by applicant]
WO 2018145649A1 · 2018 [cited by applicant]
WO 2018152181A1 · 2018 [cited by applicant]
WO 2018222935A1 · 2018 [cited by applicant]
WO 2019030240A1 · 2019 [cited by applicant]
WO 2020150339A1 · 2019 [cited by applicant]
WO 2019196713A1 · 2019 [cited by applicant]
WO 2019222275A2 · 2019 [cited by applicant]
WO 2020010235A1 · 2020 [cited by applicant]
WO 2020010284A1 · 2020 [cited by applicant]
WO 2020023888A2 · 2020 [cited by applicant]
WO 2020092654A1 · 2020 [cited by applicant]
WO 2020108646A1 · 2020 [cited by applicant]
WO 2020123691A2 · 2020 [cited by applicant]
WO 2020180591A1 · 2020 [cited by applicant]
WO 2020186204A1 · 2020 [cited by applicant]
WO WO2020247670A1 · 2020 [cited by examiner]
WO 2021008463A1 · 2021 [cited by applicant]
WO 2019152742A1 · 2021 [cited by applicant]
WO 2021179353A1 · 2021 [cited by applicant]
Abbott et al. To go or not to go? Biological logic gating engineered T cells. Immunother Cancer 10: e004185, 2022 (11 total pages). [cited by examiner]
Bhattacharya et al. Impact of genetic variation on three dimensional structure and function of proteins. PLoS ONE 12(3): e0171355, 2017. [cited by examiner]
Bork, P. Powers and pitfalls in sequence analysis: the 70% hurdle. Genome Res 10: 398-400, 2000. [cited by examiner]
Bork, P. Go hunting in sequence databases but watch out for the traps. Trends in Genetics 12(10): 425-427, 1996. [cited by examiner]
Brenner. S.E. Errors in genome annotation. Trends in Genetics 15:132-133, 1999. [cited by examiner]
Celichowski et al. Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efcacy, and fexibility. J Translat Med 21: 197, 2023 (24 total pages). [cited by examiner]
Doerks et al. Protein annotation: detective work for function prediction. Trends in Genetics 14:248-250, 1998. [cited by examiner]
Fenton et al. Rheostat positions: a new classification of protein positions relevant to pharmacogenomics. Medicinal Chem Res 29: 1133-1146, 2020. [cited by examiner]
Guo et al. Protein tolerance to random amino acid change. Proc Natl Acad Sci USA 101(25): 9205-9210, 2004. [cited by examiner]
Lin et al. Genetically Engineered Anti-CD45 Single-Chain AntibodyStreptavidin Fusion Protein for Pretargeted Radioimmunotherapy of Hematologic Malignancies. Cancer Res 66(7): 3884-3892, 2006. [cited by examiner]
Moradi-Kalbolandi et al. Development of an anti-CD45RA-quantum dots conjugated scFv to detect leukemic cancer stem cells. Mol Biol Reports 47: 225-234, 2020. [cited by examiner]
Ngo et al. “Computational complexity, protein structure prediction, and the Levinthal paradox” in The Protein Folding Problem and Tertiary Structure Prediction, pp. 492-495, 1994. [cited by examiner]
Rheinlander et al. CD45 in human physiology and clinical medicine. Immunol Lett 196: 22-32, 2018. [cited by examiner]
Rhodes et al. Activation of Human γδ T Cells by Cytosolic Interactions of BTN3A1 with Soluble Phosphoantigens and the Cytoskeletal Adaptor Periplakin. J Immunol 194: 2390-2398, 2015. [cited by examiner]
Rossotti et al. Streamlined method for parallel identification of single domain antibodies to membrane receptors on whole cells. Biochim Biophys Acta 1850: 1397-1404, 2015. [cited by examiner]
Shin et al. Characterization of Monoclonal Antibodies against Human Leukocyte Common Antigen (CD45). Immune Network 11(2): 114-122, 2011. [cited by examiner]
Shipley et al. Genome-Wide Surveillance of Genital Herpes Simplex Virus Type 1 From Multiple Anatomic Sites Over Time. J Infect Dis 218: 595-605, 2018. [cited by examiner]
Skolnick et al. From genes to protein structure and function: novel applications of computational approaches in the genomic era. Trends Biotechnol 18(I):34-39 2000. [cited by examiner]
Smith et al. The challenges of genome sequence annotation or “the devil is in the details”. Nature Biotechnol 15: 1222-1223, 1997. [cited by examiner]
Tokuriki et al. Stability effects of mutations and protein evolvability. Curr Opin Structural Biol 19: 596-604, 2009. [cited by examiner]
Wells, J.A. Additivity of mutational effects in proteins. Biochemistry 29(37): 8509-8517, 1990. [cited by examiner]
Shepherd, Philip , et al., “Monoclonal Antibodies: A Practical Approach”, Oxford University Press, 2000 (TOC). [cited by applicant]
Sommer, Cesar , et al., “Allogeneic FLT3 CAR T Cells with an Off-Switch Exhibit Potent Activity against AML and Can Be Depleted to Expedite Bone Marrow Recovery”, Molecular Therapy; Oct. 7, 2020;28(10):2237-2251. doi: 1… [cited by applicant]
Sommer, Cesar , et al., “Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma”, Molecular Therapy; Jun. 5, 2019;27(6):1126-1138. doi: 10.1016/j.ymthe.2019.04.001. Epub Ap… [cited by applicant]
Thiel, Nadine , et al., “Viral Interference with Functions of the Cellular Receptor Tyrosine Phosphatase CD45”, Viruses 2015, 7, 1540-1557; doi:10.3390/v7031540. [cited by applicant]
Tramontano, Anna , et al., “Framework Residue 71 is a Major Determinant of the Position and Conformation of the Second Hypervariable Region in the V H Domains of Immunoglobulins”, J. Mol. Biol. (1990) 215, 175-182. [cited by applicant]
Weidle, Ulrich , et al., “Proteases as Activators for Cytotoxic Prodrugs in Antitumor Therapy”, Cancer Genomics & Proteomics 11: 67-80 (2014). [cited by applicant]
Whitlow, Marc , et al., “An improved linker for single-chain Fv with reduced aggregation and enhanced proteolytic stability”, Protein Engineering; Nov. 1993;6(8):989-95. doi: 10.1093/protein/6.8.989. [cited by applicant]
Zanetti, Maurizio , et al., “The Antibodies”, vol. 1, Harwood Academic Publisher, 1995, Luxembourg (TOC). [cited by applicant]
Al-Lazikani, Bissan , et al., “Standard Conformations for the Canonical Structures of Immunoglobulins”, J. Mol. Biol. (1997) 273, 927-948. [cited by applicant]
Atkins, J. F., et al., “A case for “StopGo”: Reprogramming translation to augment codon meaning of GGN by promoting unconventional termination (Stop) after addition of glycine and then allowing continued translation (Go… [cited by applicant]
Ausubel, Frederick M., et al., “Short Protocols in Molecular Biology”, A Compendium of Methods from Current Protocols in Molecular Biology; 4th ED.; Wiley and Sons, 1999; (TOC). [cited by applicant]
Bakalar, Matthew H., et al., “Size-dependent segregation controls macrophage phagocytosis of antibody-opsonized targets”, Cell. Jun. 28, 2018; 174(1): 131-142.e13. doi:10.1016/j.cell.2018.05.059. [cited by applicant]
Bierer, B. , et al., “Cyclosporin A and FK506: molecular mechanisms of immunosuppression and probes for transplantation biology”, Current Opinion in Immunology; 1993; 5:763-773. [cited by applicant]
Catty, D. , “Antibodies: a practical approach”, IRL Press Ltd. 1988, Oxford England (TOC). [cited by applicant]
Celis, Julio E., “Cell Biology: A Laboratory Hnadbook”, Academic Press, 1998 (TOC). [cited by applicant]
Chang, Veronica T., et al., “Initiation of T cell signaling by CD45 segregation at ‘close-contacts’”, Nat Immunol. May 2016 ; 17(5): 574-582. doi: 10.1038/ni.3392. [cited by applicant]
Cho, Jae-Ho , et al., “CD45-mediated control of TCR tuning in naïve and memory CD8 + T cells”, Nat Commununications; Nov. 14, 2016;7:13373. doi: 10.1038/ncomms13373. [cited by applicant]
Chothia, Cyrus , et al., “Canonical structures for the hypervariable regions of immunoglobulins”, J Mol Biol; Aug. 20, 1987;196(4):901-17. doi: 10.1016/0022-2836(87)90412-8. [cited by applicant]
Chothia, Cyrus , et al., “Conformations of immunoglobulin hypervariable regions”, Nature. vol. 342 . 21/ Dec. 28, 1989. [cited by applicant]
Chothia, Cyrus , et al., “Structural Repertoire of the Human VH Segments”, J. Mol. Biol. (1992) 227, 799-917. [cited by applicant]
Clark, Mike , “Antibody humanization: a case of the ‘Emperor's new clothes’?”, Immunol Today; . Aug. 2000;21 (8):397-402. doi: 10.1016/s0167-5699(00)01680-7. [cited by applicant]
Coligan, John E., et al., “Current Protocols in Immunology”, vol. 1, 1991, John Wiley & Sons, Inc.(TOC). [cited by applicant]
Courtney, Adam H., et al., “CD45 functions as a signaling gatekeeper in T cells”, Sci Signal; Oct. 22, 2019;12(604):eaaw8151. doi: 10.1126/scisignal.aaw8151. [cited by applicant]
Davis, Simon , et al., “The kinetic-segregation model: TCR triggering and beyond”, Nature Immunology; vol. 7, No. 8, Aug. 2006. [cited by applicant]
Desnoyers, Luc R., “Tumor-Specific Activation of an EGFR-Targeting Probody Enhances Therapeutic Index”, Sci Transl Med. 2013. doi:10.1126/scitranslmed.3006682. [cited by applicant]
Donnelly, Michelle , et al., “Fluorescent Tagging of Herpes Simplex Virus Tegument Protein VP13/14 in Virus Infection”, Journal of Virology, vol. 75, No. 6, Mar. 2001, p. 2575-2583. [cited by applicant]
Donnelly, Michelle , et al., “Nuclear Localization and Shuttling of Herpes Simplex Virus Tegument Protein VP13/14”, Journal of Virology, vol. 75, No. 6, Mar. 2001, p. 2566-2574. [cited by applicant]
Doronina, Victoria A., et al., “Site-Specific Release of Nascent Chains from Ribosomes at a Sense Codon”, Molecular and Cellular Biology, vol. 28, No. 13, Jul. 2008, p. 4227-4239. [cited by applicant]
Doyle, Alan , et al., “Cell and Tissue Culture: Laboratory Procedures in Biotechnology”, John Wiley & Sons, Ltd., West Sussex, England, 1998 (TOC). [cited by applicant]
EPO , “International Search Report & Written Opinion”, mailed on Jun. 7, 2022 for International Application No. PCT/US2021/064615 36 pages. [cited by applicant]
Eshhar, Zelig , et al., “Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell r… [cited by applicant]
Felberg, Jackie , et al., “Characterization of Recombinant CD45 Cytoplasmic Domain Proteins”, The Journal of Biological Chemistry; vol. 273, No. 28, Issue of Jul. 10, pp. 17839-17845, 1998. [cited by applicant]
Fellouse, F. A., “High-throughput Generation of Synthetic Antibodies from Highly Functional Minimalist Phage-displayed Libraries”, J. Mol. Biol.; 2007; 373; 924-940. [cited by applicant]
Finch, Peter , “Antibodies”, 1st Ed., Stride Publications, 1997 (TOC). [cited by applicant]
Gait, M. J., “Oligonucleotide Synthesis: A Practical Approach”, IRL Press Ltd., Oxford, England, 1984 (TOC). [cited by applicant]
Gaj, Thomas , et al., “Genome-Editing Technologies: Principles and Applications”, Cold Spring Harbor Perspective in Biology; 2016;8:a023754. [cited by applicant]
Geiger, Martina , et al., “Protease-activation using anti-idiotypic masks enables tumor specificity of a folate receptor 1-T cell bispecific antibody”, Nature Communications; (2020) 11:3196 | https://doi.org/10.1038/s41… [cited by applicant]
Gialeli, Chrisostomi , et al., “Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting”, FEBS Journal 278 (2011) 16-27. [cited by applicant]
Han, Xiaolu , et al., “Masked Chimeric Antigen Receptor for Tumor-Specific Activation”, Mol Therapy; Jan. 4, 2017;25 (1):274-284. doi: 10.1016/j.ymthe.2016.10.011. Epub Jan. 4, 2017. [cited by applicant]
Harlow, Ed , et al., “Epitope Mapping”, Using Antibodies: A Laboratory Manual, Chapter 11, Cold Spring Harbor aboratory Press, NY, 1998. [cited by applicant]
Henderson, D. J., et al., “Comparison of the effects of FK-506, cyclosporin A and rapamycin on IL-2 production”, Immunology. Jul. 1991; 73(3):316-21. [cited by applicant]
Janeway, Charles A., et al., “Immunobiology”, Churchill Livingstone; 2nd Edition, Sep. 1, 1997, (TOC). [cited by applicant]
Jayasena, S. D., et al., “Aptamers: an emerging class of molecules that rival antibodies in diagnostics”, Clin Chem. Sep. 1999;45(9):1628-50. [cited by applicant]
Kabat, Elvin A., et al., “Sequences of Proteins of Immunological Interest”, 5th Ed. NIH publication, No. 91-3242; 1992 (TOC). [cited by applicant]
Ledbetter, Jeffrey A., et al., “CD45 regulates signal transduction and lymphocyte activation by specific association with receptor molecules on T or B cells”, Proc. Nati. Acad. Sci. USA; vol. 85, pp. 8628-8632, Nov. 198… [cited by applicant]
Liu, J. , et al., “Inhibition of T Cell Signaling by Immunophilin-Ligand Complexes Correlates with Loss of Calcineurin Phosphatase Activity”, Biochemistry, 1992, 31, 3891-3901. [cited by applicant]
Makabe, Koki , et al., “Thermodynamic Consequences of Mutations in Vernier Zone Residues of a Humanized Anti-human Epidermal Growth Factor Receptor Murine Antibody, 528”, The Journal of Biological Chemistry vol. 283, No… [cited by applicant]
Mather, Jennie P., et al., “Introduction to Cell and Tissue Culture: Theory and Techique”, Plem Press, New Yord, NY, 1998, (TOC). [cited by applicant]
Mcneill, Louise , et al., “The Differential Regulation of Lck Kinase Phosphorylation Sites by CD45 Is Critical for T Cell Receptor Signaling Responses”, Immunity 27, 425-437, Sep. 2007; DOI 10.1016/j.immuni.2007.07.015. [cited by applicant]
Miller, Jeffrey H., et al., “Gene Transfer Vectors for Mammalian Cells”, Current Communications in Molecular Biology, Cold Spring Harbor Laboratory, 1987 (TOC). [cited by applicant]
Mullis , et al., “PCR: The Polymerase Chain Reaction”, Birkauswer Press, Boston, 1994 (Table of Contents). [cited by applicant]
Payne, Kyle K., et al., “BTN3A1 governs anti-tumor responses by coordinating alpha-beta and gamma-delta T cells”, Science. Aug. 21, 2020; 369(6506): 942-949. doi:10.1126/science.aay2767. [cited by applicant]
Penninger, Josef M., et al., “CD45: new jobs for an old acquaintance”, Nature Immunology; May 2001;2 (5):389-96. doi: 10.1038/87687. [cited by applicant]
Poreba, Marcin , et al., “Protease-activated prodrugs: strategies, challenges, and future directions”, The FEBS Journal; vol. 287, Issue10; May 2020; pp. 1936-1969. [cited by applicant]
Razvag, Yair , et al., “Nanoscale kinetic segregation of TCR and CD45 in engaged microvilli facilitates early T cell activation”, Nature Communications; 2018, 9732; DOI: 10.1038/s41467-018-03127-w. [cited by applicant]
Remington , “The Science and Practice of Pharmacy”, 21st Ed. Mack Publishing, 2005, Table of Contents. [cited by applicant]
Sadelain, Michel , et al., “The promise and potential pitfalls of chimeric antigen receptors”, Current Opinion in Immunology 2009, 21:215-223. [cited by applicant]
Sambrook, J. , et al., “Molecular Cloning: A Laboratory Manual”, Second Ed., Cold Spring Harbor Laboratory Press, 1989 (TOC). [cited by applicant]