1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Cancer Biology
  4. Volume 4, 2020
  5. Article

Annual Review of Cancer Biology

Volume 4, 2020

Engineering T Cells to Treat Cancer: The Convergence of Immuno-Oncology and Synthetic Biology

Abstract

T cells engineered to recognize and kill tumor cells have emerged as powerful agents for combating cancer. Nonetheless, our ability to engineer T cells remains relatively primitive. Aside from CAR T cells for treating B cell malignancies, most T cell therapies are risky, toxic, and often ineffective, especially those that target solid cancers. To fulfill the promise of cell-based therapies, we must transform cell engineering into a systematic and predictable science by applying the principles and tools of synthetic biology. Synthetic biology uses a hierarchical approach—assembling sets of modular molecular parts that can be combined into larger circuits and systems that perform defined target tasks. We outline the toolkit of synthetic modules that are needed to overcome the challenges of solid cancers, progress in building these components, and how these modules could be used to reliably engineer more effective and precise T cell therapies.

Keyword(s): cellular immunotherapy, chimeric antigen receptors, engineered immune cells, solid tumors, synthetic biology, T cells
Loading

Article metrics loading...

/content/journals/10.1146/annurev-cancerbio-030419-033657
2020-03-04
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/cancerbio/4/1/annurev-cancerbio-030419-033657.html?itemId=/content/journals/10.1146/annurev-cancerbio-030419-033657&mimeType=html&fmt=ahah

Literature Cited

  1. Anderson KG, Stromnes IM, Greenberg PD 2017. Obstacles posed by the tumor microenvironment to T cell activity: a case for synergistic therapies. Cancer Cell 31:3311–25
     [Google Scholar]
  2. Bagashev A, Sotillo E, Tang C-H, Black KL, Perazzelli J et al. 2018. CD19 Alterations emerging after CD19-directed immunotherapy cause retention of the misfolded protein in the endoplasmic reticulum. Mol. Cell. Biol. 38:21e00383–18
     [Google Scholar]
  3. Baumeister SH, Murad J, Werner L, Daley H, Trebeden-Negre H et al. 2018. Phase 1 trial of autologous CAR T cells targeting NKG2D ligands in patients with AML/MDS and multiple myeloma. Cancer Immunol. Res. 7:1100–12
     [Google Scholar]
  4. Berger C, Flowers ME, Warren EH, Riddell SR 2006. Analysis of transgene-specific immune responses that limit the in vivo persistence of adoptively transferred HSV-TK-modified donor T cells after allogeneic hematopoietic cell transplantation. Blood 107:62294–302
     [Google Scholar]
  5. Bielamowicz K, Fousek K, Byrd TT, Samaha H, Mukherjee M et al. 2017. Trivalent CAR T-cells overcome interpatient antigenic variability in glioblastoma. Neuro-Oncology 20:4506–18
     [Google Scholar]
  6. Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF et al. 2018. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 24:5541–50
     [Google Scholar]
  7. Bollard CM, Rössig C, Calonge JM, Huls HM, Wagner H-J et al. 2002. Adapting a transforming growth factor β-related tumor protection strategy to enhance antitumor immunity. Blood 99:93179–87
     [Google Scholar]
  8. Bonini C, Ferrari G, Verzeletti S, Servida P, Zappone E et al. 1997. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 276:53191719–24
     [Google Scholar]
  9. Bouchkouj N, Kasamon YL, de Claro AR, George B, Lin X et al. 2018. FDA approval summary: axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma. Clin. Cancer Res. 25:61702–8
     [Google Scholar]
  10. Brentjens RJ, Davila ML, Riviere I, Park J, Wang X et al. 2013. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci. Transl. Med. 5:177177ra38
     [Google Scholar]
  11. Brown JM. 2000. Exploiting the hypoxic cancer cell: mechanisms and therapeutic strategies. Mol. Med. Today 6:4157–62
     [Google Scholar]
  12. Brudno JN, Kochenderfer JN. 2016. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood 127:263321–30
     [Google Scholar]
  13. Cameron ED, Bashor CJ, Collins JJ 2014. A brief history of synthetic biology. Nat. Rev. Microbiol. 12:5381–90
     [Google Scholar]
  14. Cartellieri M, Feldmann A, Koristka S, Arndt C, Loff S et al. 2016. Switching CAR T cells on and off: a novel modular platform for retargeting of T cells to AML blasts. Blood Cancer J 6:8e458
     [Google Scholar]
  15. Caruana I, Savoldo B, Hoyos V, Weber G, Liu H et al. 2015. Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes. Nat. Med. 21:5524–29
     [Google Scholar]
  16. Caruso HG, Hurton LV, Najjar A, Rushworth D, Ang S et al. 2015. Tuning sensitivity of CAR to EGFR density limits recognition of normal tissue while maintaining potent antitumor activity. Cancer Res 75:173505–18
     [Google Scholar]
  17. Chakravarti D, Wong WW. 2015. Synthetic biology in cell-based cancer immunotherapy. Trends Biotechnol 33:8449–61
     [Google Scholar]
  18. Chen K, Wada M, Pinz K, Liu H, Shuai X et al. 2017. A compound chimeric antigen receptor strategy for targeting multiple myeloma. Leukemia 32:2402–12
     [Google Scholar]
  19. Chen L, Flies DB. 2013. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat. Rev. Immunol. 13:4227–42
     [Google Scholar]
  20. Chen LC, Chen YY. 2019. Outsmarting and outmuscling cancer cells with synthetic and systems immunology. Curr. Opin. Biotechnol. 60:111–18
     [Google Scholar]
  21. Chen N, Li X, Chintala NK, Tano ZE, Adusumilli PS 2018. Driving CARs on the uneven road of antigen heterogeneity in solid tumors. Curr. Opin. Immunol. 51:103–10
     [Google Scholar]
  22. Cheng AA, Lu TK. 2012. Synthetic biology: an emerging engineering discipline. Annu. Rev. Biomed. Eng. 14:155–78
     [Google Scholar]
  23. Cho J, Collins JJ, Wong WW 2018. Universal chimeric antigen receptors for multiplexed and logical control of T cell responses. Cell 173:61426–38.e11
     [Google Scholar]
  24. Craddock JA, Lu A, Bear A, Pule M, Brenner MK et al. 2010. Enhanced tumor trafficking of GD2 chimeric antigen receptor T cells by expression of the chemokine receptor CCR2b. J. Immunother. 33:8780–88
     [Google Scholar]
  25. Diaconu I, Ballard B, Zhang M, Chen Y, West J et al. 2017. Inducible caspase-9 selectively modulates the toxicities of CD19-specific chimeric antigen receptor-modified T cells. Mol. Ther. 25:580–92
     [Google Scholar]
  26. Duong MT, Collinson-Pautz MR, Morschl E, Lu A, Szymanski SP et al. 2018. Two-dimensional regulation of CAR-T therapy with orthogonal switches. Mol. Ther. Oncolyt. 12:124–37
     [Google Scholar]
  27. Ebert LM, Yu W, Gargett T, Brown MP 2018. Logic-gated approaches to extend the utility of chimeric antigen receptor T-cell technology. Biochem. Soc. Trans. 46:2391–401
     [Google Scholar]
  28. Esensten JH, Bluestone JA, Lim WA 2016. Engineering therapeutic T cells: from synthetic biology to clinical trials. Annu. Rev. Pathol. Mech. Dis. 12:305–30
     [Google Scholar]
  29. Eyquem J, Mansilla-Soto J, Giavridis T, van der Stegen SJ, Hamieh M et al. 2017. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature 543:7643113–17
     [Google Scholar]
  30. Fedorov VD, Themeli M, Sadelain M 2013. PD-1– and CTLA-4–based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci. Transl. Med. 5:215215ra172
     [Google Scholar]
  31. Feucht J, Sun J, Eyquem J, Ho Y-J, Zhao Z et al. 2019. Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency. Nat. Med. 25:182–88
     [Google Scholar]
  32. Fischbach MA, Bluestone JA, Lim WA 2013. Cell-based therapeutics: the next pillar of medicine. Sci. Transl. Med. 5:179179ps7
     [Google Scholar]
  33. Foster AE, Mahendravada A, Shinners NP, Chang W-C, Crisostomo J et al. 2017. Regulated expansion and survival of chimeric antigen receptor-modified T cells using small molecule-dependent inducible MyD88/CD40. Mol. Ther. 25:2176–88
     [Google Scholar]
  34. Fraietta JA, Nobles CL, Sammons MA, Lundh S, Carty SA et al. 2018. Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells. Nature 558:7709307–12
     [Google Scholar]
  35. Fry TJ, Shah NN, Orentas RJ, Stetler-Stevenson M, Yuan CM et al. 2017. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat. Med. 24:120–28
     [Google Scholar]
  36. Geering B, Fussenegger M. 2015. Synthetic immunology: modulating the human immune system. Trends Biotechnol 33:265–79
     [Google Scholar]
  37. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D et al. 2012. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 366:10883–92
     [Google Scholar]
  38. Gilham DE, Maher J. 2017. ‘Atypical’ CAR T cells: NKG2D and Erb-B as examples of natural receptor/ligands to target recalcitrant solid tumors. Immunotherapy 9:9723–33
     [Google Scholar]
  39. Griffith JW, Sokol CL, Luster AD 2014. Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu. Rev. Immunol. 32:659–702
     [Google Scholar]
  40. Harlin H, Meng Y, Peterson AC, Zha Y, Tretiakova M et al. 2009. Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment. Cancer Res 69:73077–85
     [Google Scholar]
  41. Hegde M, Mukherjee M, Grada Z, Pignata A, Landi D et al. 2016. Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape. J. Clin. Investig. 126:83036–52
     [Google Scholar]
  42. Ho P-C, Bihuniak J, Macintyre AN, Staron M, Liu X et al. 2015. Phosphoenolpyruvate is a metabolic checkpoint of anti-tumor T cell responses. Cell 162:61217–28
     [Google Scholar]
  43. Idorn M, thor Straten P 2018. Chemokine receptors and exercise to tackle the inadequacy of T cell homing to the tumor site. Cells 7:8108
     [Google Scholar]
  44. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N 2002. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. PNAS 99:1912293–97
     [Google Scholar]
  45. Jerby-Arnon L, Shah P, Cuoco MS, Rodman C, Su M-J et al. 2018. A cancer cell program promotes T cell exclusion and resistance to checkpoint blockade. Cell 175:4984–97.e24
     [Google Scholar]
  46. Johnson LA, Morgan RA, Dudley ME, Cassard L, Yang JC et al. 2009. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 114:3535–46
     [Google Scholar]
  47. June CH, Warshauer JT, Bluestone JA 2017. Is autoimmunity the Achilles’ heel of cancer immunotherapy. ? Nat. Med. 23:5540–47
     [Google Scholar]
  48. Kawalekar OU, O'Connor RS, Fraietta JA, Guo L, McGettigan SE et al. 2016. Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T cells. Immunity 44:2380–90
     [Google Scholar]
  49. Kershaw MH, Wang G, Westwood JA, Pachynski RK, Tiffany LH et al. 2002. Redirecting migration of T cells to chemokine secreted from tumors by genetic modification with CXCR2. Hum. Gene Ther. 13:161971–80
     [Google Scholar]
  50. Kitada T, DiAndreth B, Teague B, Weiss R 2018. Programming gene and engineered-cell therapies with synthetic biology. Science 359:6376eaad1067
     [Google Scholar]
  51. Klampatsa A, Achkova DY, Davies DM, Parente-Pereira AC, Woodman N et al. 2017. Intracavitary ‘T4 immunotherapy’ of malignant mesothelioma using pan-ErbB re-targeted CAR T-cells. Cancer Lett 393:52–59
     [Google Scholar]
  52. Klebanoff CA, Rosenberg SA, Restifo NP 2016. Prospects for gene-engineered T cell immunotherapy for solid cancers. Nat. Med. 22:126–36
     [Google Scholar]
  53. Kloss CC, Condomines M, Cartellieri M, Bachmann M, Sadelain M 2013. Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Nat. Biotechnol. 31:171–75
     [Google Scholar]
  54. Kloss CC, Lee J, Zhang A, Chen F, Melenhorst J et al. 2018. Dominant negative TGF-β receptor enhances PSMA targeted human CAR T cell proliferation and augments tumor eradication in prostate cancer. Mol. Ther. 26:1855–66
     [Google Scholar]
  55. Knaus P, Lindemann D, DeCoteau J, Perlman R, Yankelev H et al. 1996. A dominant inhibitory mutant of the type II transforming growth factor beta receptor in the malignant progression of a cutaneous T-cell lymphoma. Mol. Cell. Biol. 16:73480–89
     [Google Scholar]
  56. Kochenderfer JN, Dudley ME, Feldman SA, Wilson WH, Spaner DE et al. 2012. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood 119:122709–20
     [Google Scholar]
  57. Kretz-Rommel A, Qin F, Dakappagari N, Ravey PE, McWhirter J et al. 2007. CD200 expression on tumor cells suppresses antitumor immunity: new approaches to cancer immunotherapy. J. Immunol. 178:95595–605
     [Google Scholar]
  58. Kudo K, Imai C, Lorenzini P, Kamiya T, Kono K et al. 2014. T lymphocytes expressing a CD16 signaling receptor exert antibody-dependent cancer cell killing. Cancer Res 74:193–103
     [Google Scholar]
  59. Le RQ, Li L, Yuan W, Shord SS, Nie L et al. 2018. FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell‐induced severe or life‐threatening cytokine release syndrome. Oncology 23:8943–47
     [Google Scholar]
  60. Leach DR, Krummel MF, Allison JP 1996. Enhancement of antitumor immunity by CTLA-4 blockade. Science 271:52561734–36
     [Google Scholar]
  61. Lee L, Draper B, Chaplin N, Philip B, Chin M et al. 2017. An APRIL based chimeric antigen receptor for dual targeting of BCMA and TACI in multiple myeloma. Blood 131:7746–58
     [Google Scholar]
  62. Levine BL, Miskin J, Wonnacott K, Keir C 2017. Global manufacturing of CAR T cell therapy. Mol. Ther. Methods Clin. Dev. 4:92–101
     [Google Scholar]
  63. Li MO, Wan YY, Sanjabi S, Robertson A-KL, Flavell RA 2006. Transforming growth factor-β regulation of immune responses. Annu. Rev. Immunol. 24:99–146
     [Google Scholar]
  64. Lim WA, June CH. 2017. The principles of engineering immune cells to treat cancer. Cell 168:4724–40
     [Google Scholar]
  65. Linette GP, Stadtmauer EA, Maus MV, Rapoport AP, Levine BL et al. 2013. Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood 122:6863–71
     [Google Scholar]
  66. Liu X, Jiang S, Fang C, Yang S, Olalere D et al. 2015. Affinity-tuned ErbB2 or EGFR chimeric antigen receptor T cells exhibit an increased therapeutic index against tumors in mice. Cancer Res 75:173596–607
     [Google Scholar]
  67. Liu X, Ranganathan R, Jiang S, Fang C, Sun J et al. 2016. A chimeric switch-receptor targeting PD1 augments the efficacy of second-generation CAR T cells in advanced solid tumors. Cancer Res 76:61578–90
     [Google Scholar]
  68. Long AH, Haso WM, Shern JF, Wanhainen KM, Murgai M et al. 2015. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat. Med. 21:6581–90
     [Google Scholar]
  69. Lynn RC, Weber EW, Gennert D, Sotillo E, Xu P et al. 2019. C-Jun overexpressing CAR-T cells are exhaustion-resistant and mediate enhanced antitumor activity. bioRxiv 653725. https://doi.org/10.1101/653725
    [Crossref]
  70. Ma JS, Kim J, Kazane SA, Choi S, Yun H et al. 2016. Versatile strategy for controlling the specificity and activity of engineered T cells. PNAS 113:4E450–58
     [Google Scholar]
  71. Mariathasan S, Turley SJ, Nickles D, Castiglioni A, Yuen K et al. 2018. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature 554:7693544–48
     [Google Scholar]
  72. Maude SL, Barrett D, Teachey DT, Grupp SA 2014a. Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J 20:2119–22
     [Google Scholar]
  73. McGranahan N, Swanton C. 2015. Biological and therapeutic impact of intratumor heterogeneity in cancer evolution. Cancer Cell 27:115–26
     [Google Scholar]
  74. McGranahan N, Swanton C. 2017. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell 168:4613–28
     [Google Scholar]
  75. Menger L, Sledzinska A, Bergerhoff K, Vargas F, Smith J et al. 2016. TALEN-mediated inactivation of PD-1 in tumor-reactive lymphocytes promotes intratumoral T-cell persistence and rejection of established tumors. Cancer Res 76:82087–93
     [Google Scholar]
  76. Moon EK, Carpenito C, Sun J, Wang L-CS, Kapoor V et al. 2011. Expression of a functional CCR2 receptor enhances tumor localization and tumor eradication by retargeted human T cells expressing a mesothelin-specific chimeric antibody receptor. Clin. Cancer Res. 17:144719–30
     [Google Scholar]
  77. Morgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF et al. 2013. Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J. Immunother. 36:2133–51
     [Google Scholar]
  78. Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA 2010. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol. Ther. 18:4843–51
     [Google Scholar]
  79. Morsut L, Roybal KT, Xiong X, Gordley RM, Coyle SM et al. 2016. Engineering customized cell sensing and response behaviors using synthetic Notch receptors. Cell 164:4780–91
     [Google Scholar]
  80. Newick K, O'Brien S, Moon E, Albelda SM 2016. CAR T cell therapy for solid tumors. Annu. Rev. Med. 68:139–52
     [Google Scholar]
  81. Oda SK, Daman AW, Garcia NM, Wagener F, Schmitt T et al. 2017. A CD200R-CD28 fusion protein appropriates an inhibitory signal to enhance T-cell function and therapy of murine leukemia. Blood 130:222410–19
     [Google Scholar]
  82. O'Leary MC, Lu X, Huang Y, Lin X, Mahmood I et al. 2018. FDA approval summary: tisagenlecleucel for treatment of patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Clin. Cancer Res. 25:41142–46
     [Google Scholar]
  83. Orlando EJ, Han X, Tribouley C, Wood PA, Leary RJ et al. 2018. Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia. Nat. Med. 24:101504–6
     [Google Scholar]
  84. O'Rourke DM, Nasrallah MP, Desai A, Melenhorst JJ, Mansfield K et al. 2017. 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. 9:399eaaa0984
     [Google Scholar]
  85. Park JH, Geyer MB, Brentjens RJ 2016. CD19-targeted CAR T-cell therapeutics for hematologic malignancies: interpreting clinical outcomes to date. Blood 127:263312–20
     [Google Scholar]
  86. Park JS, Rhau B, Hermann A, McNally KA, Zhou C et al. 2014. Synthetic control of mammalian-cell motility by engineering chemotaxis to an orthogonal bioinert chemical signal. PNAS 111:165896–901
     [Google Scholar]
  87. Park K, Kim S, Bang Y, Park J, Kim N et al. 1994. Genetic changes in the transforming growth factor beta (TGF-beta) type II receptor gene in human gastric cancer cells: correlation with sensitivity to growth inhibition by TGF-beta. PNAS 91:198772–76
     [Google Scholar]
  88. Parkhurst MR, Yang JC, Langan RC, Dudley ME, Nathan D-AN et al. 2011. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol. Ther. 19:3620–26
     [Google Scholar]
  89. Pearce EL, Poffenberger MC, Chang C-H, Jones RG 2013. Fueling immunity: insights into metabolism and lymphocyte function. Science 342:61551242454
     [Google Scholar]
  90. Peranzoni E, Rivas-Caicedo A, Bougherara H, Salmon H, Donnadieu E 2013. Positive and negative influence of the matrix architecture on antitumor immune surveillance. Cell Mol. Life Sci. 70:234431–48
     [Google Scholar]
  91. Philip B, Kokalaki E, Mekkaoui L, Thomas S, Straathof K et al. 2014. A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy. Blood 124:81277–87
     [Google Scholar]
  92. Porter D, Frey N, Wood PA, Weng Y, Grupp SA 2018. Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel. J. Hematol. Oncol. 11:135
     [Google Scholar]
  93. Qasim W, Zhan H, Samarasinghe S, Adams S, Amrolia P et al. 2017. Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Sci. Transl. Med. 9:374eaaj2013
     [Google Scholar]
  94. Qin H, Ramakrishna S, Nguyen S, Fountaine TJ, Ponduri A et al. 2018. Preclinical development of bivalent chimeric antigen receptors targeting both CD19 and CD22. Mol. Ther. Oncolyt. 11:127–37
     [Google Scholar]
  95. Rabinovich GA, Gabrilovich D, Sotomayor EM 2007. Immunosuppressive strategies that are mediated by tumor cells. Annu. Rev. Immunol. 25:267–96
     [Google Scholar]
  96. Rafiq S, Yeku OO, Jackson HJ, Purdon TJ, van Leeuwen DG et al. 2018. Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo. Nat. Biotechnol. 36:9847–56
     [Google Scholar]
  97. Rodgers DT, Mazagova M, Hampton EN, Cao Y, Ramadoss NS et al. 2016. Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies. PNAS 113:4E459–68
     [Google Scholar]
  98. Rosenberg SA, Restifo NP. 2015. Adoptive cell transfer as personalized immunotherapy for human cancer. Science 348:623062–68
     [Google Scholar]
  99. Roybal KT, Lim WA. 2017. Synthetic immunology: hacking immune cells to expand their therapeutic capabilities. Annu. Rev. Immunol. 35:229–53
     [Google Scholar]
  100. Roybal KT, Rupp LJ, Morsut L, Walker WJ, McNally KA et al. 2016a. Precision tumor recognition by T cells with combinatorial antigen-sensing circuits. Cell 164:4770–79
     [Google Scholar]
  101. Roybal KT, Williams JZ, Morsut L, Rupp LJ, Kolinko I et al. 2016b. Engineering T cells with customized therapeutic response programs using synthetic Notch receptors. Cell 167:2419–32.e16
     [Google Scholar]
  102. Ruella M, Barrett DM, Kenderian SS, Shestova O, Hofmann TJ et al. 2016. Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. J. Clin. Investig. 126:103814–26
     [Google Scholar]
  103. Rupp LJ, Schumann K, Roybal KT, Gate RE, Ye CJ et al. 2017. CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells. Sci. Rep. 7:737
     [Google Scholar]
  104. Sachdeva M, Duchateau P, Depil S, Poirot L, Valton J 2019. Granulocyte-macrophage colony-stimulating factor inactivation in CAR T-cells prevents monocyte-dependent release of key cytokine release syndrome mediators. J. Biol. Chem. 294:145430–37
     [Google Scholar]
  105. Salmon H, Franciszkiewicz K, Damotte D, Dieu-Nosjean M-C, Validire P et al. 2012. Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors. J. Clin. Investig. 122:3899–910
     [Google Scholar]
  106. Sarkar RR, Gloude NJ, Schiff D, Murphy JD 2018. Cost-effectiveness of chimeric antigen receptor T-cell therapy in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia. J. Natl. Cancer Inst. 111:7719–26
     [Google Scholar]
  107. Schultz L, Davis KL, Baggott C, Chaudry C, Marcy A et al. 2018. Phase 1 study of CD19/CD22 bispecific chimeric antigen receptor (CAR) therapy in children and young adults with B cell acute lymphoblastic leukemia (ALL). Blood 132:Suppl. 1898
     [Google Scholar]
  108. Sigalotti L, Fratta E, Coral S, Tanzarella S, Danielli R et al. 2004. Intratumor heterogeneity of cancer/testis antigens expression in human cutaneous melanoma is methylation-regulated and functionally reverted by 5-Aza-2′-deoxycytidine. Cancer Res 64:249167–71
     [Google Scholar]
  109. Slaney CY, Kershaw MH, Darcy PK 2014. Trafficking of T cells into tumors. Cancer Res 74:247168–74
     [Google Scholar]
  110. Slaney CY, von Scheidt B, Davenport AJ, Beavis PA, Westwood JA et al. 2017. Dual-specific chimeric antigen receptor T cells and an indirect vaccine eradicate a variety of large solid tumors in an immunocompetent, self-antigen setting. Clin. Cancer Res. 23:102478–90
     [Google Scholar]
  111. Sotillo E, Barrett DM, Black KL, Bagashev A, Oldridge D et al. 2015. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discov 5:121282–95
     [Google Scholar]
  112. Stasi A, Angelis B, Rooney CM, Zhang L, Mahendravada A et al. 2009. T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood 113:256392–402
     [Google Scholar]
  113. Stasi A, Tey S-K, Dotti G, Fujita Y, Kennedy-Nasser A et al. 2011. Inducible apoptosis as a safety switch for adoptive cell therapy. N. Engl. J. Med. 365:181673–83
     [Google Scholar]
  114. Stavrou M, Philip B, Traynor-White C, Davis CG, Onuoha S et al. 2018. A rapamycin activated caspase 9 based suicide gene. Mol. Ther. 26:1266–76
     [Google Scholar]
  115. Stone JD, Aggen DH, Schietinger A, Schreiber H, Kranz DM 2012. A sensitivity scale for targeting T cells with chimeric antigen receptors (CARs) and bispecific T-cell engagers (BiTEs). Oncoimmunology 1:6863–73
     [Google Scholar]
  116. Straathof KC, Pulè MA, Yotnda P, Dotti G, Vanin EF et al. 2005. An inducible caspase 9 safety switch for T-cell therapy. Blood 105:114247–54
     [Google Scholar]
  117. Suarez E, Chang D-K, Sun J, Sui J, Freeman GJ et al. 2016. Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model. Oncotarget 7:2334341–55
     [Google Scholar]
  118. Valton J, Guyot V, Boldajipour B, Sommer C, Pertel T et al. 2018. A versatile safeguard for chimeric antigen receptor T-cell immunotherapies. Sci. Rep. 8:8972
     [Google Scholar]
  119. Viaud S, Ma JS, Hardy IR, Hampton EN, Benish B et al. 2018. Switchable control over in vivo CAR T expansion, B cell depletion, and induction of memory. PNAS 115:46E10898–906
     [Google Scholar]
  120. Vormittag P, Gunn R, Ghorashian S, Veraitch FS 2018. A guide to manufacturing CAR T cell therapies. Curr. Opin. Biotechnol. 53:164–81
     [Google Scholar]
  121. Walker AJ, Majzner RG, Zhang L, Wanhainen K, Long AH et al. 2017. Tumor antigen and receptor densities regulate efficacy of a chimeric antigen receptor targeting anaplastic lymphoma kinase. Mol. Ther. 25:2189–201
     [Google Scholar]
  122. Wang R, Green DR. 2012. Metabolic checkpoints in activated T cells. Nat. Immunol. 13:10907–15
     [Google Scholar]
  123. Wang X, Chang W-C, Wong CW, Colcher D, Sherman M et al. 2011. A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood 118:51255–63
     [Google Scholar]
  124. Watanabe K, Kuramitsu S, Posey AD, June CH 2018. Expanding the therapeutic window for CAR T cell therapy in solid tumors: the knowns and unknowns of CAR T cell biology. Front. Immunol. 9:2486
     [Google Scholar]
  125. Wilkie S, van Schalkwyk MC, Hobbs S, Davies DM, van der Stegen SJ et al. 2012. Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling. J. Clin. Immunol. 32:51059–70
     [Google Scholar]
  126. Wu C-Y, Roybal KT, Puchner EM, Onuffer J, Lim WA 2015a. Remote control of therapeutic T cells through a small molecule–gated chimeric receptor. Science 350:6258aab4077
     [Google Scholar]
  127. Wu C-Y, Rupp LJ, Roybal KT, Lim WA 2015b. Synthetic biology approaches to engineer T cells. Curr. Opin. Immunol. 35:123–30
     [Google Scholar]
  128. Yamamoto TN, Lee P-H, Vodnala SK, Gurusamy D, Kishton RJ et al. 2019. T cells genetically engineered to overcome death signaling enhance adoptive cancer immunotherapy. J. Clin. Investig. 129:1551–65
     [Google Scholar]
  129. Yang Y, Jacoby E, Fry TJ 2015. Challenges and opportunities of allogeneic donor-derived CAR T cells. Curr. Opin. Hematol. 22:6509–15
     [Google Scholar]
  130. Zah E, Lin M-Y, Silva-Benedict A, Jensen MC, Chen YY 2016. T cells expressing CD19/CD20 bispecific chimeric antigen receptors prevent antigen escape by malignant B cells. Cancer Immunol. Res. 4:6498–508
     [Google Scholar]
  131. Zhang H, Snyder KM, Suhoski MM, Maus MV, Kapoor V et al. 2007. 4-1BB is superior to CD28 costimulation for generating CD8+ cytotoxic lymphocytes for adoptive immunotherapy. J. Immunol. 179:74910–18
     [Google Scholar]
  132. Zhao J, Song Y, Liu D 2019. Clinical trials of dual-target CAR T cells, donor-derived CAR T cells, and universal CAR T cells for acute lymphoid leukemia. J. Hematol. Oncol. 12:117
     [Google Scholar]
/content/journals/10.1146/annurev-cancerbio-030419-033657
Loading
Engineering T Cells to Treat Cancer: The Convergence of Immuno-Oncology and Synthetic Biology
Annual Review of Cancer Biology 4, 121 (2020); https://doi.org/10.1146/annurev-cancerbio-030419-033657
/content/journals/10.1146/annurev-cancerbio-030419-033657
/content/journals/10.1146/annurev-cancerbio-030419-033657
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error