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Review

Novel approaches to promote CAR T-cell function in solid tumors

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Pages 789-799 | Received 17 Feb 2019, Accepted 29 Apr 2019, Published online: 10 May 2019

References

  • Kuwana Y, Asakura Y, Utsunomiya N, et al. Expression of chimeric receptor composed of immunoglobulin-derived V regions and T-cell receptor-derived C regions. Biochem Biophys Res Commun. 1987;149(3):960–968.
  • Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A. 1989;86(24):10024–10028.
  • Finney HM, Lawson AD, Bebbington CR, et al. Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product. J Immunol. 1998;161(6):2791–2797.
  • Finney HM, Akbar AN, Lawson AD. Activation of resting human primary T cells with chimeric receptors: costimulation from CD28, inducible costimulator, CD134, and CD137 in series with signals from the TCR zeta chain. J Immunol. 2004;172(1):104–113.
  • Maher J, Brentjens RJ, Gunset G, et al. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta/CD28 receptor. Nat Biotechnol. 2002;20(1):70–75.
  • Haynes NM, Trapani JA, Teng MWL, et al. Single-chain antigen recognition receptors that costimulate potent rejection of established experimental tumors. Blood. 2002;100(9):3155–3163.
  • Haynes NM, Trapani JA, Teng MWL, et al. Rejection of syngeneic colon carcinoma by CTLs expressing single-chain antibody receptors codelivering CD28 costimulation. J Immunol. 2002;169(10):5780–5786.
  • Imai C, Mihara K, Andreansky M, et al. Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia. 2004;18(4):676–684.
  • Brentjens RJ, Santos E, Nikhamin Y, et al. et al., Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts. Clin Cancer Res. 2007;13(18 Pt 1):5426–5435.
  • Kochenderfer JN, Wilson WH, Janik JE, et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood. 2010;116(20):4099–4102.
  • Porter DL, Levine BL, Kalos M, et al. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011;365(8):725–733.
  • Kalos M, Levine BL, Porter DL, 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.
  • Feins S, Kong W, Williams EF, et al. An introduction to Chimeric Antigen Receptor (CAR) T cell immunotherapy for human cancer. Am J Hematol. 2019;94:S3–S9.
  • Park JH, Rivière I, Gonen M, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378(5):449–459.
  • Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018;378(5):439–448.
  • Lee DW, Kochenderfer JN, Stetler-Stevenson M, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385(9967):517–528.
  • Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-Cell lymphoma. N Engl J Med. 2019;380(1):45–56.
  • Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019;20(1):31–42.
  • Turtle CJ, Breen M, Choyke P, et al. Immunotherapy of non-Hodgkin‘s lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells. Sci Transl Med. 2016;8(355):355ra116.
  • Brudno, JN, Maric I, Hartman SD, et al. T cells genetically modified to express an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma. J Clin Oncol. 2018;36:JCO2018778084.
  • Prasad V. Immunotherapy: tisagenlecleucel - the first approved CAR-T-cell therapy: implications for payers and policy makers. Nat Rev Clin Oncol. 2018;15(1):11–12.
  • Knochelmann HM, Smith AS, Dwyer CJ, et al. CAR T cells in solid tumors: blueprints for building effective therapies. Front Immunol. 2018;9:1740.
  • Pule MA, Straathof KC, Dotti G, et al. A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells. Mol Ther. 2005;12(5):933–941.
  • Chmielewski M, Kopecky C, Hombach AA, et al. IL-12 release by engineered T cells expressing chimeric antigen receptors can effectively Muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression. Cancer Res. 2011;71(17):5697–5706.
  • Pegram HJ, Lee JC, Hayman EG, et al. Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning. Blood. 2012;119(18):4133–4141.
  • Kershaw MH, Westwood JA, Parker LL, et al. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res. 2006;12(20 Pt 1):6106–6115.
  • Bonifant CL, Jackson HJ, Brentjens RJ, et al. Toxicity and management in CAR T-cell therapy. Mol Ther Oncolytics. 2016;3:16011.
  • Lamers CH, Klaver Y, Gratama JW, et al. Treatment of metastatic renal cell carcinoma (mRCC) with CAIX CAR-engineered T-cells-a completed study overview. Biochem Soc Trans. 2016;44(3):951–959.
  • Lamers CH, Sleijfer S, Vulto AG, et al. Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience. J Clin Oncol. 2006;24(13):e20–2.
  • Lamers CH, Sleijfer S, van Steenbergen S, et al. Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation and management of on-target toxicity. Mol Ther. 2013;21(4):904–912.
  • Morgan RA, Yang JC, Kitano M, et al. 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.
  • Heslop HE. Safer CARS. Mol Ther. 2010;18(4):661–662.
  • Parente-Pereira AC, Burnet J, Ellison D, et al. Trafficking of CAR-engineered human T cells following regional or systemic adoptive transfer in SCID beige mice. J Clin Immunol. 2011;31(4):710–718.
  • Brown CE, Alizadeh D, Starr R, et al. Regression of glioblastoma after chimeric antigen receptor T-cell therapy. N Engl J Med. 2016;375(26):2561–2569.
  • Krause A, Guo HF, Latouche JB, et al. Antigen-dependent CD28 signaling selectively enhances survival and proliferation in genetically modified activated human primary T lymphocytes. J Exp Med. 1998;188(4):619–626.
  • Wilkie S, van Schalkwyk MCI, Hobbs S, et al. Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling. J Clin Immunol. 2012;32(5):1059–1070.
  • Kloss CC, Condomines M, Cartellieri M, et al. Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Nat Biotechnol. 2013;31(1):71–75.
  • Roybal KT, Rupp LJ, Morsut L, et al. Precision Tumor Recognition by T Cells With Combinatorial Antigen-Sensing Circuits. Cell. 2016;164(4):770–779.
  • Roybal KT, Williams JZ, Morsut L, et al. Engineering T Cells with Customized Therapeutic Response Programs Using Synthetic Notch Receptors. Cell. 2016;167(2):419–432. e16.
  • Orlando EJ, Han X, Tribouley C, et al. Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia. Nat Med. 2018;24(10):1504–1506.
  • Fedorov VD, Themeli M, Sadelain M. PD-1- and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci Transl Med. 2013;5(215):215ra172.
  • Chicaybam L, Bonamino MH, Construction and validation of an activating and inhibitory chimeric antigen receptor (CAR) system Proceedings of the American Association for Cancer Research Meeting, Philadelphia, Pennsylvania. Abstract number 3156, 2015.
  • Vogelstein B, Papadopoulos N, Velculescu VE, et al. Cancer genome landscapes. Science. 2013;339(6127):1546–1558.
  • Burchell J, Poulsom R, Hanby A, et al. An alpha2,3 sialyltransferase (ST3Gal I) is elevated in primary breast carcinomas. Glycobiology. 1999;9(12):1307–1311.
  • Wilkie S, Picco G, Foster J, et al. Retargeting of human T cells to tumor-associated MUC1: the evolution of a chimeric antigen receptor. J Immunol. 2008;180(7):4901–4909.
  • Maher J, Wilkie S. CAR mechanics: driving T cells into the MUC of cancer. Cancer Res. 2009;69(11):4559–4562.
  • Posey AD Jr., Schwab RD, Boesteanu AC, et al. Engineered CAR T cells targeting the cancer-associated tn-glycoform of the membrane mucin MUC1 control adenocarcinoma. Immunity. 2016;44(6):1444–1454.
  • Sugawa N, Ekstrand AJ, James CD, et al. Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc Natl Acad Sci U S A. 1990;87(21):8602–8606.
  • Sok JC, Coppelli FM, Thomas SM, et al. Mutant epidermal growth factor receptor (EGFRvIII) contributes to head and neck cancer growth and resistance to EGFR targeting. Clin Cancer Res. 2006;12(17):5064–5073.
  • Rae JM, Scheys JO, Clark KM, et al. EGFR and EGFRvIII expression in primary breast cancer and cell lines. Breast Cancer Res Treat. 2004;87(1):87–95.
  • Okamoto I, Kenyon LC, Emlet DR, et al. Expression of constitutively activated EGFRvIII in non-small cell lung cancer. Cancer Sci. 2003;94(1):50–56.
  • Moscatello DK, Holgado-Madruga M, Godwin AK, et al. Frequent expression of a mutant epidermal growth factor receptor in multiple human tumors. Cancer Res. 1995;55(23):5536–5539.
  • O‘Rourke, DM, Nasrallah MP, Desai A, et al. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. 2017;9(399):eaaa0984.
  • Schneider D, Xiong Y, Wu D, et al. A tandem CD19/CD20 CAR lentiviral vector drives on-target and off-target antigen modulation in leukemia cell lines. J Immunother Cancer. 2017;5:42.
  • Chong EA, Svoboda J, Nasta SD, et al. Sequential Anti-CD19 Directed Chimeric Antigen Receptor Modified T-Cell Therapy (CART19) and PD-1 Blockade with Pembrolizumab in Patients with Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas. Blood. 2018;132(4198). https://doi.org/10.1182/blood-2018-99-119502.
  • Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell. 2006;124(2):263–266.
  • Shiga K, Hara M, Nagasaki T, et al. Cancer-Associated Fibroblasts: their Characteristics and Their Roles in Tumor Growth. Cancers (Basel). 2015;7(4):2443–2458.
  • Provenzano PP, Inman DR, Eliceiri KW, et al. Collagen density promotes mammary tumor initiation and progression. BMC Med. 2008;6:11.
  • Salmon H, Franciszkiewicz K, Damotte D, et al. Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors. J Clin Invest. 2012;122(3):899–910.
  • Adachi K, Kano Y, Nagai T, et al. IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor. Nat Biotechnol. 2018;36(4):346–351.
  • Cathcart J, Pulkoski-Gross A, Cao J. Targeting matrix metalloproteinases in cancer: bringing new life to old ideas. Genes Dis. 2015;2(1):26–34.
  • Devy L, Huang L, Naa L, et al. Selective inhibition of matrix metalloproteinase-14 blocks tumor growth, invasion, and angiogenesis. Cancer Res. 2009;69(4):1517–1526.
  • Mardomi A, Abediankenari S. Matrix Metalloproteinase 8: could it Benefit the CAR-T Cell Therapy of Solid Tumors?- a- Commentary on Therapeutic Potential. Cancer Microenviron. 2018;11(1):93–96.
  • Caruana I, Savoldo B, Hoyos V, et al. Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes. Nat Med. 2015;21(5):524–529.
  • Curiel TJ, Coukos G, Zou L, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10(9):942–949.
  • Li Y–Q, Liu -F-F, Zhang X-M, et al. Tumor secretion of CCL22 activates intratumoral Treg infiltration and is independent prognostic predictor of breast cancer. PLoS One. 2013;8(10):e76379.
  • Mantovani A, Sozzani S, Locati M, et al. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002;23(11):549–555.
  • Strauss L, Bergmann C, Gooding W, et al. The frequency and suppressor function of CD4+CD25highFoxp3+ T cells in the circulation of patients with squamous cell carcinoma of the head and neck. Clin Cancer Res. 2007;13(21):6301–6311.
  • Liu VC, Wong LY, Jang T, et al. Tumor evasion of the immune system by converting CD4+CD25- T cells into CD4+CD25+ T regulatory cells: role of tumor-derived TGF-beta. J Immunol. 2007;178(5):2883–2892.
  • Pandiyan P, Zheng L, Ishihara S, et al. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol. 2007;8(12):1353–1362.
  • Fallarino F, Grohmann U, You S, et al. The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol. 2006;176(11):6752–6761.
  • Raskovalova T, Lokshin A, Huang X, et al. Inhibition of cytokine production and cytotoxic activity of human antimelanoma specific CD8+ and CD4+ T lymphocytes by adenosine-protein kinase A type I signaling. Cancer Res. 2007;67(12):5949–5956.
  • Newick K, O’Brien S, Sun J, et al. Augmentation of CAR T-cell Trafficking and Antitumor Efficacy by Blocking Protein Kinase A Localization. Cancer Immunol Res. 2016;4(6):541–551.
  • Di Stasi A, De Angelis B, Rooney CM, et al. T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood. 2009;113(25):6392–6402.
  • Bollard CM, Rössig C, Calonge MJ, et al. Adapting a transforming growth factor beta-related tumor protection strategy to enhance antitumor immunity. Blood. 2002;99(9):3179–3187.
  • Kloss CC, Lee J, Zhang A, et al. Dominant-Negative TGF-β Receptor Enhances PSMA-Targeted Human CAR T Cell Proliferation And Augments Prostate Cancer Eradication. Mol Ther. 2018;26(7):1855–1866.
  • Chang ZL, Lorenzini MH, Chen X, et al. Rewiring T-cell responses to soluble factors with chimeric antigen receptors. Nat Chem Biol. 2018;14(3):317–324.
  • Hou AJ, Chang ZL, Lorenzini MH, et al. TGF-beta-responsive CAR-T cells promote anti-tumor immune function. Bioeng Transl Med. 2018;3(2):75–86.
  • Sukumaran S, Watanabe N, Bajgain P, et al. Enhancing the Potency and Specificity of Engineered T Cells for Cancer Treatment. Cancer Discov. 2018;8(8):972–987.
  • Lo AS, Taylor JR, Farzaneh F, et al. Harnessing the tumour-derived cytokine, CSF-1, to co-stimulate T-cell growth and activation. Mol Immunol. 2008;45(5):1276–1287.
  • Wilkie S, Burbridge SE, Chiapero-Stanke L, et al. Selective expansion of chimeric antigen receptor-targeted T-cells with potent effector function using interleukin-4. J Biol Chem. 2010;285(33):25538–25544.
  • Leen AM, Sukumaran S, Watanabe N, et al. Reversal of tumor immune inhibition using a chimeric cytokine receptor. Mol Ther. 2014;22(6):1211–1220.
  • Beavis PA, Henderson MA, Giuffrida L, et al. Targeting the adenosine 2A receptor enhances chimeric antigen receptor T cell efficacy. J Clin Invest. 2017;127(3):929–941.
  • Markley JC, Sadelain M. IL-7 and IL-21 are superior to IL-2 and IL-15 in promoting human T cell-mediated rejection of systemic lymphoma in immunodeficient mice. Blood. 2010;115(17):3508–3519.
  • Hurton LV, Singh H, Najjar AM, et al. Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells. Proc Natl Acad Sci U S A. 2016;113(48): E7788-E7797.
  • Koneru M, Sevko A, Heide J, et al. IL-12 secreting tumor-targeted chimeric antigen receptor T cells eradicate ovarian tumors in vivo. Oncoimmunology. 2015;4(3):e994446.
  • Zhang L, Morgan RA, Beane JD, et al. Tumor-infiltrating lymphocytes genetically engineered with an inducible gene encoding interleukin-12 for the immunotherapy of metastatic melanoma. Clin Cancer Res. 2015;21(10):2278–2288.
  • Koneru M, Presnell S, Domico K, et al. A phase I clinical trial of adoptive T cell therapy using IL-12 secreting MUC-16(ecto) directed chimeric antigen receptors for recurrent ovarian cancer. J Transl Med. 2015;13:102.
  • Hu B, Ren J, Luo Y, et al. Augmentation of Antitumor Immunity by Human and Mouse CAR T Cells Secreting IL-18. Cell Rep. 2017;20(13):3025–3033.
  • Chmielewski M, Abken H. CAR T Cells Releasing IL-18 Convert to T-Bet(high) FoxO1(low) Effectors that Exhibit Augmented Activity against Advanced Solid Tumors. Cell Rep. 2017;21(11):3205–3219.
  • Carroll RG, Carpenito C, Shan X, et al. Distinct Effects of IL-18 on the Engraftment and Function of Human Effector CD8+ T Cells and Regulatory T Cells. PLoS One. 2008;3(9):e3289.
  • Avanzi MP, Yeku O, Li X, et al. Engineered Tumor-Targeted T Cells Mediate Enhanced Anti-Tumor Efficacy Both Directly and through Activation of the Endogenous Immune System. Cell Rep. 2018;23(7):2130–2141.
  • Eales KL, Hollinshead KE, Tennant DA. Hypoxia and metabolic adaptation of cancer cells. Oncogenesis. 2016;5:e190.
  • Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029–1033.
  • Le Bourgeois T, Strauss L, Aksoylar H-I, et al. Targeting T Cell Metabolism for Improvement of Cancer Immunotherapy. Front Oncol. 2018;8:237.
  • Noman MZ, Desantis G, Janji B, et al. PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med. 2014;211(5):781–790.
  • Corzo CA, Condamine T, Lu L, et al. HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med. 2010;207(11):2439–2453.
  • Schmielau J, Finn OJ. Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of t-cell function in advanced cancer patients. Cancer Res. 2001;61(12):4756–4760.
  • Kawalekar OU, O’Connor RS, Fraietta JA, et al. Distinct Signaling of Coreceptors Regulates Specific Metabolism Pathways and Impacts Memory Development in CAR T Cells. Immunity. 2016;44(2):380–390.
  • van der Windt GJ, Everts B, Chang C-H, et al. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity. 2012;36(1):68–78.
  • Juillerat A, Marechal A, Filhol JM, et al. An oxygen sensitive self-decision making engineered CAR T-cell. Sci Rep. 2017;7:39833.
  • Gowrishankar K, Birtwistle L, Micklethwaite K. Manipulating the tumor microenvironment by adoptive cell transfer of CAR T-cells. Mamm Genome. 2018;29(11–12):739–756.
  • Ando T, Mimura K, Johansson CC, et al. Transduction with the antioxidant enzyme catalase protects human T cells against oxidative stress. J Immunol. 2008;181(12):8382–8390.
  • Ligtenberg MA, Mougiakakos D, Mukhopadhyay M, et al. Coexpressed Catalase Protects Chimeric Antigen Receptor-Redirected T Cells as well as Bystander Cells from Oxidative Stress-Induced Loss of Antitumor Activity. J Immunol. 2016;196(2):759–766.
  • O‘Sullivan D, Pearce EL. Targeting T cell metabolism for therapy. Trends Immunol. 2015;36(2):71–80.
  • Speiser DE, Ho PC, Verdeil G. Regulatory circuits of T cell function in cancer. Nat Rev Immunol. 2016;16(10):599–611.
  • Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350–1355.
  • Chambers CA, Kuhns MS, Egen JG, et al. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol. 2001;19:565–594.
  • Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271(5256):1734–1736.
  • Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–723.
  • Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–2526.
  • Ribas A, Camacho LH, Lopez-Berestein G, et al. Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. J Clin Oncol. 2005;23(35):8968–8977.
  • Condomines M, Arnason J, Benjamin R, et al. Tumor-Targeted Human T Cells Expressing CD28-Based Chimeric Antigen Receptors Circumvent CTLA-4 Inhibition. PLoS One. 2015;10(6):e0130518.
  • Zou W, Wolchok JD, Chen L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations. Sci Transl Med. 2016;8(328):328rv4.
  • Parry RV, Chemnitz JM, Frauwirth KA, et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol. 2005;25(21):9543–9553.
  • John LB, Devaud C, Duong CPM, 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.
  • Chong EA, Melenhorst JJ, Lacey SF, et al. PD-1 blockade modulates chimeric antigen receptor (CAR)-modified T cells: refueling the CAR. Blood. 2017;129(8):1039–1041.
  • Cherkassky L, Morello A, Villena-Vargas J, et al. Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. J Clin Invest. 2016;126(8):3130–3144.
  • Rafiq S, Yeku OO, Jackson HJ, et al. Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo. Nat Biotechnol. 2018;36(9):847–856.
  • Liu X, Ranganathan R, Jiang S, 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.
  • Yin Y, Boesteanu AC, Binder ZA, et al. Checkpoint Blockade Reverses Anergy in IL-13Ralpha2 Humanized scFv-Based CAR T Cells to Treat Murine and Canine Gliomas. Mol Ther Oncolytics. 2018;11:20–38.
  • Zhao J, Lin Q, Song Y, et al. Universal CARs, universal T cells, and universal CAR T cells. J Hematol Oncol. 2018;11(1):132.
  • Torikai H, Reik A, Soldner F, et al. Toward eliminating HLA class I expression to generate universal cells from allogeneic donors. Blood. 2013;122(8):1341–1349.
  • Torikai H, Reik A, Liu P-Q, et al. A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR. Blood. 2012;119(24):5697–5705.
  • Poirot L, Philip B, Schiffer-Mannioui C, et al. Multiplex Genome-Edited T-cell Manufacturing Platform for “Off-the-Shelf” Adoptive T-cell Immunotherapies. Cancer Res. 2015;75(18):3853–3864.
  • Ren J, Liu X, Fang C, et al. Multiplex Genome Editing to Generate Universal CAR T Cells Resistant to PD1 Inhibition. Clin Cancer Res. 2017;23(9):2255–2266.
  • Ren J, Zhang X, Liu X, et al. A versatile system for rapid multiplex genome-edited CAR T cell generation. Oncotarget. 2017;8(10):17002–17011.
  • Liu X, Zhang Y, Cheng C, et al. CRISPR-Cas9-mediated multiplex gene editing in CAR-T cells. Cell Res. 2017;27(1):154–157.
  • Zhang Y, Zhang X, Cheng C, et al. CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells. Front Med. 2017;11(4):554–562.
  • Urbanska K, Lanitis E, Poussin M, et al. A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor. Cancer Res. 2012;72(7):1844–1852.
  • Lohmueller JJ, Ham JD, Kvorjak M, et al. mSA2 affinity-enhanced biotin-binding CAR T cells for universal tumor targeting. Oncoimmunology. 2017;7(1):e1368604.
  • Cho JH, Collins JJ, Wong WW. Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses. Cell. 2018;173(6): 1426–1438. e11.
  • Zhang T, Lemoi BA, Sentman CL. Chimeric NK-receptor-bearing T cells mediate antitumor immunotherapy. Blood. 2005;106(5):1544–1551.

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