A chimeric switch-receptor targeting PD1 augments the efficacy of second-generation CAR T cells in advanced solid tumors

Cancer Research

Volumn 76, Issue 6, 2016, Pages 1578-1590

  Liu, Xiaojun ^a   Ranganathan, Raghuveer ^b   Jiang, Shuguang ^a   Fang, Chongyun ^a   Sun, Jing ^b   Kim, Soyeon ^b   Newick, Kheng ^b   Lo, Albert ^c   June, Carl H ^a   Zhao, Yangbing ^a   Moon, Edmund K ^b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARCINOEMBRYONIC ANTIGEN RELATED CELL ADHESION MOLECULE 1; CD28 ANTIGEN; CHIMERIC ANTIGEN RECEPTOR; GAMMA INTERFERON; INHIBITORY RECEPTOR; LENTIVIRUS VECTOR; PD1 ANTIBODY; PEMBROLIZUMAB; PROGRAMMED DEATH 1 RECEPTOR; PROTEIN ANTIBODY; TIM3 PROTEIN; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; LYMPHOCYTE ANTIGEN RECEPTOR; TUMOR ANTIGEN;

ADOPTIVE IMMUNOTHERAPY; ADVANCED CANCER; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER IMMUNOTHERAPY; CANCER INFILTRATION; CANCER MORTALITY; CELL EXPANSION; CELLULAR IMMUNITY; CONTROLLED STUDY; CYTOKINE RELEASE; EX VIVO STUDY; GENE CONSTRUCT; GENE THERAPY; GENETIC ENGINEERING; HUMAN; HUMAN CELL; IN VITRO STUDY; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN MOTIF; PROTEIN TARGETING; SOLID TUMOR; T LYMPHOCYTE; TUMOR CELL DESTRUCTION; TUMOR VOLUME; UPREGULATION; VIRAL GENE DELIVERY SYSTEM; ANIMAL; DRUG SCREENING; FEMALE; IMMUNOLOGY; K-562 CELL LINE; NEOPLASM; NONOBESE DIABETIC MOUSE; PROCEDURES; SCID MOUSE; SIGNAL TRANSDUCTION; TUMOR ASSOCIATED LEUKOCYTE; TUMOR CELL LINE;

ANIMALS; ANTIGENS, CD28; ANTIGENS, NEOPLASM; CELL LINE, TUMOR; FEMALE; HUMANS; IMMUNOTHERAPY, ADOPTIVE; K562 CELLS; LYMPHOCYTES, TUMOR-INFILTRATING; MICE; MICE, INBRED NOD; MICE, SCID; NEOPLASMS; PROGRAMMED CELL DEATH 1 RECEPTOR; RECEPTORS, ANTIGEN, T-CELL; SIGNAL TRANSDUCTION; T-LYMPHOCYTES; TUMOR BURDEN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84962163731     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-15-2524     Document Type: Article

References (54)

1. Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res 2011; 17: 4550-7.
2. Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor modified T cells in chronic lymphoid leukemia. N Engl J Med 2011; 365: 725-33.
3. Govers C, Sebestyen Z, Coccoris M, Willemsen RA, Debets R. Tcell receptor gene therapy: strategies for optimizing transgenic TCR pairing. Trends Mol Med 2010; 16: 77-87.
4. Chmielewski M, Hombach AA, Abken H. Antigen-specific T-cell activation independently of the MHC: chimeric antigen receptor-redirected T cells. Front Immunol 2013; 4: 371.
5. Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 2013; 368: 1509-18.
6. Tlsty TD, Coussens LM. Tumor stroma and regulation of cancer development. Annu Rev Pathol 2006; 1: 119-50.
7. Waldmann TA Effective cancer therapy through immunomodulation. Annu Rev Med 2006; 57: 65-81.
8. Al-Zoughbi W, Huang J, Paramasivan GS, Till H, Pichler M, Guertl-Lackner B, et al. Tumor macroenvironment and metabolism. Semin Oncol 2014; 41: 281-95.
9. Denko NC Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nat Rev Cancer 2008; 8: 705-13.
10. Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol 2013; 14: 1014-22.
11. Zheng Y, Zha Y, Gajewski TF. Molecular regulation of T-cell anergy. EMBO Rep 2008; 9: 50-5.
12. Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 2008; 8: 467-77.
13. Kamphorst AO, Ahmed R. Manipulating the PD-1 pathway to improve immunity. Curr Opin Immunol 2013; 25: 381-8.
14. Chemnitz JM, Parry RV, Nichols KE, June CH, Riley JL. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J Immunol 2004; 173: 945-54.
15. Dai S, Jia R, Zhang X, Fang Q, Huang L. The PD-1/PD-Ls pathway and autoimmune diseases. Cell Immunol 2014; 290: 72-9.
16. Konishi J, Yamazaki K, Azuma M, Kinoshita I, Dosaka-Akita H, Nishimura M. B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clin Cancer Res 2004; 10: 5094-100.
17. Ahmadzadeh M, Johnson LA, Heemskerk B, Wunderlich JR, Dudley ME, White DE, et al. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 2009; 114: 1537-44.
18. Gao Q, Wang XY, Qiu SJ, Yamato I, Sho M, Nakajima Y, et al. Over expression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res 2009; 15: 971-9.
19. Thompson RH, Dong H, Lohse CM, Leibovich BC, Blute ML, Cheville JC, et al. PD-1 isexpressed bytumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. Clin Cancer Res 2007; 13: 1757-61.
20. Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol 2015; 33: 1974-82.
21. Moon EK, Wang LC, Dolfi DV, Wilson CB, Ranganathan R, Sun J, et al. Multifactorial T-cell hypofunction that is reversible can limit the efficacy of chimeric antigen receptor-transduced human T cells in solid tumors. Clin Cancer Res 2014; 20: 4262-73.
22. Ankri C, Shamalov K, Horovitz-Fried M, Mauer S, Cohen CJ. Human T cells engineered to express a programmed death 1/28 costimulatory retargeting molecule display enhanced antitumor activity. J Immunol 2013; 191: 4121-9.
23. Kobold S, Grassmann S, Chaloupka M, Lampert C, Wenk S, Kraus F, et al. Impact of a new fusion receptor on PD-1-mediated immunosuppression in adoptive T cell therapy. J Natl Cancer Inst 2015; 107: 1-10.
24. Prosser ME, Brown CE, Shami AF, Forman SJ, Jensen MC. Tumor PD-L1 costimulates primary human CD8(+) cytotoxic T cells modified to express a PD1:CD28 chimeric receptor. Mol Immunol 2012; 51: 263-72.
25. Carpenito C, Milone MC, Hassan R, Simonet JC, Lakhal M, Suhoski MM, et al. Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains. Proc Natl Acad Sci U S A 2009; 106: 3360-5.
26. Ho M, Feng M, Fisher RJ, Rader C, Pastan I. A novel high-affinity human monoclonal antibody to mesothelin. Int J Cancer 2011; 128: 2020-30.
27. Kochenderfer JN, Feldman SA, Zhao Y, Xu H, Black MA, Morgan RA, et al. Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor. J Immunother 2009; 32: 689-702.
28. Abate-Daga D, Lagisetty KH, Tran E, Zheng Z, Gattinoni L, Yu Z, et al. A novel chimeric antigen receptor against prostate stem cell antigen mediates tumor destruction in a humanized mouse model of pancreatic cancer. Hum Gene Ther 2014; 25: 1003-12.
29. Zhao Y, Moon E, Carpenito C, Paulos CM, Liu X, Brennan AL, et al. Multiple injections of electroporated autologous T cells expressing a chimeric antigenreceptor mediate regressionofhuman disseminatedtumor. Cancer Res 2010; 70: 9053-61.
30. Eshhar Z, Waks T, Gross G, Schindler DG. 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 receptors. Proc Natl Acad Sci U S A 1993; 90: 720-4.
31. Kakarla S, Gottschalk S. CAR T cells for solid tumors: armed and ready to go? Cancer J 2014; 20: 151-5.
32. Crespo J, Sun H, Welling TH, Tian Z, Zou W. T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment. Curr Opin Immunol 2013; 25: 214-21.
33. Koneru M, Schaer D, Monu N, Ayala A, Frey AB. Defective proximal TCR signaling inhibits CD8+ tumor-infiltrating lymphocyte lytic function. J Immunol 2005; 174: 1830-40.
34. Monu N, Frey AB. Suppression of proximal T cell receptor signaling and lytic function in CD8+ tumor-infiltrating T cells. Cancer Res 2007; 67: 11447-54.
35. Radoja S, Frey AB. Cancer-induced defective cytotoxic T lymphocyte effector function: another mechanism how antigenic tumors escape immune-mediated killing. Mol Med 2000; 6: 465-79.
36. Schietinger A, Greenberg PD. Tolerance and exhaustion: defining mechanisms of T cell dysfunction. Trends Immunol 2014; 35: 51-60.
37. Schlosser HA, Theurich S, Shimabukuro-Vornhagen A, Holtick U, Stippel DL, von Bergwelt-Baildon M. Overcoming tumor-mediated immunosuppression. Immunotherapy 2014; 6: 973-88.
38. Stewart TJ, Smyth MJ. Improving cancer immunotherapy by targeting tumor-induced immune suppression. Cancer Metastasis Rev 2011; 30: 125-40.
39. Vazquez-Cintron EJ, Monu NR, Frey AB. Tumor-induced disruption of proximal TCR-mediated signal transduction in tumor-infiltrating CD8+ lymphocytes inactivates antitumor effector phase. J Immunol 2010; 185: 7133-40.
40. Pardoll DM The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12: 252-64.
41. Ito T, Ueno T, Clarkson MR, Yuan X, Jurewicz MM, Yagita H, et al. Analysis of the role of negative T cell costimulatory pathways in CD4 and CD8 T cell-mediated alloimmune responses in vivo. J Immunol 2005; 174: 6648-56.
42. Blank C, Mackensen A. Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion. Cancer Immunol Immunother 2007; 56: 739-45.
43. Okosuka T, Takamatsu M, Kobayashi-Imanishi W, Hashimoto-Tane A, Azuma M, Saito T. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med 2012; 209: 1201-17.
44. Curran MA, Montalvo W, Yagita H, Allison JP. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A 2010; 107: 4275-80.
45. Fourcade J, Sun Z, Benallaoua M, Guillaume P, Luescher IF, Sander C, et al. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients. J Exp Med Sep 2010; 207: 2175-86.
46. Matsuzaki J, Gnjatic S, Mhawech-Fauceglia P, Beck A, Miller A, Tsuji T, et al. Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proc Natl Acad Sci U S A 2010; 107: 7875-80.
47. Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, Anderson AC. Targeting Tim-3 and PD-1 pathwaysto reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med 2010; 207: 2187-94.
48. Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ, et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res 2012; 72: 917-27.
49. Huang YH, Zhu C, Kondo Y, Anderson AC, Gandhi A, Russell A, et al. CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature 2015; 517: 386-90.
50. Condomines M, Arnason J, Benjamin R, Gunset G, Plotkin J, Sadelain M. Tumor-targeted human T cells expressing CD28-based chimeric antigen receptors circumvent CTLA-4 inhibition. PLoS One 2015; 10: 1-15.
51. Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther 2010; 18: 843-51.
52. Jena B, Dotti G, Cooper LJ. Redirecting T-cell specificity by introducing a tumor-specific chimeric antigen receptor. Blood 2010; 116: 1035-44.
53. Nguyen LT, Ohashi PS. Clinical blockade of PD1 and LAG3-potential mechanisms of action. Nat Rev Immunol 2015; 15: 45-56.
54. de la Rosa M, Rutz S, Dorninger H, Scheffold A. Interleukin-2 is essential for CD4+CD25+ regulatory T cell function. Eur J Immunol 2004; 34: 2480-8.