Targeting the adenosine 2A receptor enhances chimeric antigen receptor T cell efficacy

Journal of Clinical Investigation

Volumn 127, Issue 3, 2017, Pages 929-941

  Beavis, Paul A ^a,b   Henderson, Melissa A ^a,b   Giuffrida, Lauren ^a,b   Mills, Jane K ^a,b   Sek, Kevin ^a,b   Cross, Ryan S ^a,b   Davenport, Alexander J ^a,b   John, Liza B ^a,b   Mardiana, Sherly ^a,b   Slaney, Clare Y ^a,b   Johnstone, Ricky W ^a,b   Trapani, Joseph A ^a,b   Stagg, John ^c,d   Loi, Sherene ^a,b   Kats, Lev ^a,b   Gyorki, David ^a   Kershaw, Michael H ^a,b,e   Darcy, Phillip K ^a,b,e  

^a PETER MACCALLUM CANCER CENTRE   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c CENTRE HOSPITALIER DE L UNIVERSITÉ DE MONTRÉAL   (Canada)

^d UNIVERSITÉ DE MONTRÉAL   (Canada)

^e MONASH UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE A2 RECEPTOR; ADENOSINE RECEPTOR BLOCKING AGENT; CHIMERIC ANTIGEN RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; GAMMA INTERFERON; INTERLEUKIN 2; PROGRAMMED DEATH 1 RECEPTOR; SHORT HAIRPIN RNA; TUMOR NECROSIS FACTOR; ADENOSINE A2A RECEPTOR; ERBB2 PROTEIN, HUMAN; ERBB2 PROTEIN, MOUSE; HYBRID PROTEIN; LYMPHOCYTE ANTIGEN RECEPTOR;

ADOPTIVE TRANSFER; ANIMAL CELL; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; CYTOKINE PRODUCTION; FLOW CYTOMETRY; FLUORESCENCE ACTIVATED CELL SORTING; GROWTH INHIBITION; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNE DEFICIENCY; MALE; MOUSE; NONHUMAN; POLYMERASE CHAIN REACTION; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TUMOR GROWTH; TUMOR MICROENVIRONMENT; ANIMAL; CD4+ T LYMPHOCYTE; FEMALE; GENETICS; IMMUNOLOGY; MAMMARY NEOPLASMS, EXPERIMENTAL;

ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; FEMALE; HUMANS; MAMMARY NEOPLASMS, EXPERIMENTAL; MICE; RECEPTOR, ADENOSINE A2A; RECEPTOR, ERBB-2; RECEPTORS, ANTIGEN, T-CELL; RECOMBINANT FUSION PROTEINS;

EID: 85015877195     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI89455     Document Type: Article

References (67)

1. Rosenberg SA, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011;17(13):4550-4557.
2. Figlin RA, et al. Treatment of metastatic renal cell carcinoma with nephrectomy, interleukin-2 and cytokine-primed or CD8(+) selected tumor infiltrating lymphocytes from primary tumor. J Urol. 1997;158(3 pt 1):740-745.
3. Quattrocchi KB, et al. Pilot study of local autologous tumor infiltrating lymphocytes for the treatment of recurrent malignant gliomas. J Neurooncol. 1999;45(2):141-157.
4. Morgan RA, et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science. 2006;314(5796):126-129.
5. 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(2):720-724.
6. Finney HM, Lawson AD, Bebbington CR, Weir AN. Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product. J Immunol. 1998;161(6):2791-2797.
7. Carpenito C, 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(9):3360-3365.
8. Zhong XS, Matsushita M, Plotkin J, Riviere I, Sadelain M. Chimeric antigen receptors combining 4-1BB and CD28 signaling domains augment PI3kinase/AKT/Bcl-XL activation and CD8+ T cell-mediated tumor eradication. Mol Ther. 2010;18(2):413-420.
9. Tammana S, et al. 4-1BB and CD28 signaling plays a synergistic role in redirecting umbilical cord blood T cells against B-cell malignancies. Hum Gene Ther. 2010;21(1):75-86.
10. Maude SL, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507-1517.
11. Kalos M, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011;3(95):95ra73.
12. 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(8):725-733.
13. Kershaw MH, Westwood JA, Darcy PK. Geneengineered T cells for cancer therapy. Nat Rev Cancer. 2013;13(8):525-541.
14. Beavis PA, Slaney CY, Kershaw MH, Gyorki D, Neeson PJ, Darcy PK. Reprogramming the tumor microenvironment to enhance adoptive cellular therapy. Semin Immunol. 2016;28(1):64-72.
15. Beavis PA, Slaney CY, Kershaw MH, Neeson PJ, Darcy PK. Enhancing the efficacy of adoptive cellular therapy by targeting tumorinduced immunosuppression. Immunotherapy. 2015;7(5):499-512.
16. John LB, et al. Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells. Clin Cancer Res. 2013;19(20):5636-5646.
17. Liu X, et al. A chimeric switch-receptor targeting PD1 augments the efficacy of second-generation CAR T cells in advanced solid tumors. Cancer Res. 2016;76(6):1578-1590.
18. Ohta A, et al. A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci U S A. 2006;103(35):13132-13137.
19. Beavis PA, Stagg J, Darcy PK, Smyth MJ. CD73: a potent suppressor of antitumor immune responses. Trends Immunol. 2012;33(5):231-237.
20. Loi S, et al. CD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancer. Proc Natl Acad Sci U S A. 2013;110(27):11091-11096.
21. Leclerc BG, et al. CD73 Expression Is an Independent Prognostic Factor in Prostate Cancer. Clin Cancer Res. 2016;22(1):158-166.
22. Turcotte M, et al. CD73 is associated with poor prognosis in high-grade serous ovarian cancer. Cancer Res. 2015;75(21):4494-4503.
23. Stagg J, et al. Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis. Proc Natl Acad Sci U S A. 2010;107(4):1547-1552.
24. Jin D, et al. CD73 on tumor cells impairs antitumor T-cell responses: a novel mechanism of tumor-induced immune suppression. Cancer Res. 2010;70(6):2245-2255.
25. Häusler SF, et al. Anti-CD39 and anti-CD73 antibodies A1 and 7G2 improve targeted therapy in ovarian cancer by blocking adenosinedependent immune evasion. Am J Transl Res. 2014;6(2):129-139.
26. Michaud M, et al. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science. 2011;334(6062):1573-1577.
27. Hatfield SM, et al. Immunological mechanisms of the antitumor effects of supplemental oxygenation. Sci Transl Med. 2015;7(277):277ra30.
28. Sitkovsky MV, Hatfield S, Abbott R, Belikoff B, Lukashev D, Ohta A. Hostile, hypoxia-A2-adenosinergic tumor biology as the next barrier to overcome for tumor immunologists. Cancer Immunol Res. 2014;2(7):598-605.
29. Sitkovsky MV, Kjaergaard J, Lukashev D, Ohta A. Hypoxia-adenosinergic immunosuppression: tumor protection by T regulatory cells and cancerous tissue hypoxia. Clin Cancer Res. 2008;14(19):5947-5952.
30. Leone RD, Lo YC, Powell JD. A2aR antagonists: Next generation checkpoint blockade for cancer immunotherapy. Comput Struct Biotechnol J. 2015;13:265-272.
31. Waickman AT, Alme A, Senaldi L, Zarek PE, Horton M, Powell JD. Enhancement of tumor immunotherapy by deletion of the A2A adenosine receptor. Cancer Immunol Immunother. 2012;61(6):917-926.
32. Beavis PA, et al. Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors. Proc Natl Acad Sci U S A. 2013;110(36):14711-14716.
33. Beavis PA, et al. Adenosine Receptor 2A blockade increases the efficacy of anti-PD-1 through enhanced antitumor T-cell responses. Cancer Immunol Res. 2015;3(5):506-517.
34. Hauser RA, et al. Tozadenant (SYN115) in patients with Parkinson's disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial. Lancet Neurol. 2014;13(8):767-776.
35. Beavis PA, et al. CD73: A potential biomarker for anti-PD-1 therapy. Oncoimmunology. 2015;4(11):e1046675.
36. Wang LX, et al. Tumor ablation by gene-modified T cells in the absence of autoimmunity. Cancer Res. 2010;70(23):9591-9598.
37. Cekic C, Day YJ, Sag D, Linden J. Myeloid expression of adenosine A2A receptor suppresses T and NK cell responses in the solid tumor microenvironment. Cancer Res. 2014;74(24):7250-7259.
38. Allard B, Beavis PA, Darcy PK, Stagg J. Immunosuppressive activities of adenosine in cancer. Curr Opin Pharmacol. 2016;29:7-16.
39. Gao ZW, Dong K, Zhang HZ. The roles of CD73 in cancer. Biomed Res Int. 2014;2014:460654.
40. Yu YI, et al. Ecto-5nucleotidase expression is associated with the progression of renal cell carcinoma. Oncol Lett. 2015;9(6):2485-2494.
41. Zhang B, et al. High expression of CD39/ENTPD1 in malignant epithelial cells of human rectal adenocarcinoma. Tumour Biol. 2015;36(12):9411-9419.
42. Leclerc BG, et al. CD73 expression is an independent prognostic factor in prostate cancer. Clin Cancer Res. 2016;22(1):158-166.
43. Iannone R, Miele L, Maiolino P, Pinto A, Morello S. Adenosine limits the therapeutic effectiveness of anti-CTLA4 mAb in a mouse melanoma model. Am J Cancer Res. 2014;4(2):172-181.
44. Allard B, Pommey S, Smyth MJ, Stagg J. Targeting CD73 enhances the antitumor activity of anti-PD-1 and anti-CTLA-4 mAbs. Clin Cancer Res. 2013;19(20):5626-5635.
45. 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(4):843-851.
46. Ahmed N, et al. Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma. J Clin Oncol. 2015;33(15):1688-1696.
47. Lappas CM, Rieger JM, Linden J. A2A adenosine receptor induction inhibits IFN production in murine CD4+ T cells. J Immunol. 2005;174(2):1073-1080.
48. Fredholm BB, Arslan G, Halldner L, Kull B, Schulte G, Wasserman W. Structure and function of adenosine receptors and their genes. Naunyn Schmiedebergs Arch Pharmacol. 2000;362(4-5):364-374.
49. Zaretsky JM, et al. Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma. N Engl J Med. 2016;375(9):819-829.
50. Gao J, et al. Loss of IFN pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy. Cell. 2016;167(2):397-404.e9.
51. Shi LZ, et al. Interdependent IL-7 and IFN signalling in T-cell controls tumour eradication by combined CTLA-4+PD-1 therapy. Nat Commun. 2016;7:12335.
52. Wall EA, et al. Suppression of LPS-induced TNF-α production in macrophages by cAMP is mediated by PKA-AKAP95-p105. Sci Signal. 2009;2(75):ra28.
53. Moeller M, et al. Adoptive transfer of geneengineered CD4+ helper T cells induces potent primary and secondary tumor rejection. Blood. 2005;106(9):2995-3003.
54. Adusumilli PS, et al. Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. Sci Transl Med. 2014;6(261):261ra151.
55. Sommermeyer D, et al. Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo. Leukemia. 2016;30(2):492-500.
56. Zarek PE, et al. A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells. Blood. 2008;111(1):251-259.
57. Ohta A, Kini R, Ohta A, Subramanian M, Madasu M, Sitkovsky M. The development and immunosuppressive functions of CD4(+) CD25(+) FoxP3(+) regulatory T cells are under influence of the adenosine-A2A adenosine receptor pathway. Front Immunol. 2012;3:190.
58. Naganuma M, Wiznerowicz EB, Lappas CM, Linden J, Worthington MT, Ernst PB. Cutting edge: critical role for A2A adenosine receptors in the T cell-mediated regulation of colitis. J Immunol. 2006;177(5):2765-2769.
59. Chapuis AG, et al. Combined IL-21-primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient. J Exp Med. 2016;213(7):1133-1139.
60. Chapuis AG, et al. T-cell therapy using interleukin-21-primed cytotoxic T-cell lymphocytes combined with cytotoxic T-cell lymphocyte antigen-4 blockade results in long-term cell persistence durable tumor regression. J Clin Oncol. 2016;34(31): 3787-3795.
61. Johnstone CN, et al. Functional and molecular characterisation of EO771.LMB tumours, a new C57BL/6-mouse-derived model of spontaneously metastatic mammary cancer. Dis Model Mech. 2015;8(3):237-251.
62. Shiloni E, et al. Retroviral transduction of interferon-cDNA into a nonimmunogenic murine fibrosarcoma: generation of T cells in draining lymph nodes capable of treating established parental metastatic tumor. Cancer Immunol Immunother. 1993;37(5):286-292.
63. Kershaw MH, et al. Gene-engineered T cells as a superior adjuvant therapy for metastatic cancer. J Immunol. 2004;173(3):2143-2150.
64. Haynes NM, et al. Redirecting mouse CTL against colon carcinoma: superior signaling efficacy of single-chain variable domain chimeras containing TCR-vs FcRI-. J Immunol. 2001;166(1):182-187.
65. Darcy PK, et al. Redirected perforin-dependent lysis of colon carcinoma by ex vivo genetically engineered CTL. J Immunol. 2000;164(7):3705-3712.
66. Chang K, Marran K, Valentine A, Hannon GJ. Packaging shRNA retroviruses. Cold Spring Harb Protoc. 2013;2013(8):734-737.
67. Westwood JA, et al. Adoptive transfer of T cells modified with a humanized chimeric receptor gene inhibits growth of Lewis-Y-expressing tumors in mice. Proc Natl Acad Sci U S A. 2005;102(52):19051-19056.