1932

Abstract

Engineered T cells are currently in clinical trials to treat patients with cancer, solid organ transplants, and autoimmune diseases. However, the field is still in its infancy. The design, and manufacturing, of T cell therapies is not standardized and is performed mostly in academic settings by competing groups. Reliable methods to define dose and pharmacokinetics of T cell therapies need to be developed. As of mid-2016, there are no US Food and Drug Administration (FDA)–approved T cell therapeutics on the market, and FDA regulations are only slowly adapting to the new technologies. Further development of engineered T cell therapies requires advances in immunology, synthetic biology, manufacturing processes, and government regulation. In this review, we outline some of these challenges and discuss the contributions that pathologists can make to this emerging field.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-pathol-052016-100304
2017-01-24
2024-10-07
Loading full text...

Full text loading...

/deliver/fulltext/pathol/12/1/annurev-pathol-052016-100304.html?itemId=/content/journals/10.1146/annurev-pathol-052016-100304&mimeType=html&fmt=ahah

Literature Cited

  1. Barrett DM, Grupp SA, June CH. 1.  2015. Chimeric antigen receptor- and TCR-modified T cells enter Main Street and Wall Street. J. Immunol. 195:755–61 [Google Scholar]
  2. Depil S, Deconinck E, Milpied N, Sutton L, Witz F. 2.  et al. 2004. Donor lymphocyte infusion to treat relapse after allogeneic bone marrow transplantation for myelodysplastic syndrome. Bone Marrow Transplant 33:531–34 [Google Scholar]
  3. Kolb HJ, Schmid C, Barrett AJ, Schendel DJ. 3.  2004. Graft-versus-leukemia reactions in allogeneic chimeras. Blood 103:767–76 [Google Scholar]
  4. Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL. 4.  et al. 1988. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N. Engl. J. Med. 319:1676–80 [Google Scholar]
  5. Feldman SA, Assadipour Y, Kriley I, Goff SL, Rosenberg SA. 5.  2015. Adoptive cell therapy—tumor-infiltrating lymphocytes, T-cell receptors, and chimeric antigen receptors. Semin. Oncol. 42:626–39 [Google Scholar]
  6. Yannelli JR, Hyatt C, McConnell S, Hines K, Jacknin L. 6.  et al. 1996. Growth of tumor-infiltrating lymphocytes from human solid cancers: summary of a 5-year experience. Int. J. Cancer 65:413–21 [Google Scholar]
  7. Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC. 7.  et al. 2006. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314:126–29 [Google Scholar]
  8. Johnson LA, Morgan RA, Dudley ME, Cassard L, Yang JC. 8.  et al. 2009. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 114:535–46 [Google Scholar]
  9. Robbins PF, Kassim SH, Tran TL, Crystal JS, Morgan RA. 9.  et al. 2015. A pilot trial using lymphocytes genetically engineered with an NY-ESO-1-reactive T-cell receptor: long-term follow-up and correlates with response. Clin. Cancer Res. 21:1019–27 [Google Scholar]
  10. Rapoport AP, Stadtmauer EA, Binder-Scholl GK, Goloubeva O, Vogl DT. 10.  et al. 2015. NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat. Med. 21:914–21 [Google Scholar]
  11. Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL. 11.  et al. 2013. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N. Engl. J. Med. 368:1509–18 [Google Scholar]
  12. Porter DL, Hwang WT, Frey NV, Lacey SF, Shaw PA. 12.  et al. 2015. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci. Transl. Med. 7:303ra139 [Google Scholar]
  13. Maude SL, Teachey DT, Porter DL, Grupp SA. 13.  2015. CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood 125:4017–23 [Google Scholar]
  14. Garfall AL, Maus MV, Hwang WT, Lacey SF, Mahnke YD. 14.  et al. 2015. Chimeric antigen receptor T cells against CD19 for multiple myeloma. N. Engl. J. Med. 373:1040–47 [Google Scholar]
  15. Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C. 15.  et al. 2015. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 385:517–28 [Google Scholar]
  16. Brentjens RJ, Davila ML, Riviere I, Park J, Wang X. 16.  et al. 2013. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci. Transl. Med. 5:177ra38 [Google Scholar]
  17. Srivastava S, Riddell SR. 17.  2015. Engineering CAR-T cells: design concepts. Trends Immunol 36:494–502 [Google Scholar]
  18. Maus MV, Fraietta JA, Levine BL, Kalos M, Zhao Y, June CH. 18.  2014. Adoptive immunotherapy for cancer or viruses. Annu. Rev. Immunol. 32:189–225 [Google Scholar]
  19. Barrett DM, Singh N, Porter DL, Grupp SA, June CH. 19.  2014. Chimeric antigen receptor therapy for cancer. Annu. Rev. Med. 65:333–47 [Google Scholar]
  20. Liu X, Jiang S, Fang C, Yang S, Olalere D. 20.  et al. 2015. Affinity-tuned ErbB2 or EGFR chimeric antigen receptor T cells exhibit an increased therapeutic index against tumors in mice. Cancer Res 75:3596–607 [Google Scholar]
  21. Johnson LA, Scholler J, Ohkuri T, Kosaka A, Patel PR. 21.  et al. 2015. Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma. Sci. Transl. Med. 7:275ra22 [Google Scholar]
  22. Hudecek M, Sommermeyer D, Kosasih PL, Silva-Benedict A, Liu L. 22.  et al. 2015. The nonsignaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity. Cancer Immunol. Res. 3:125–35 [Google Scholar]
  23. Kawalekar OU, O'Connor RS, Fraietta JA, Guo L, McGettigan SE. 23.  et al. 2016. Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T cells. Immunity 44:380–90 [Google Scholar]
  24. Scholler J, Brady TL, Binder-Scholl G, Hwang WT, Plesa G. 24.  et al. 2012. Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells. Sci. Transl. Med. 4:132ra53 [Google Scholar]
  25. Brusko TM, Putnam AL, Bluestone JA. 25.  2008. Human regulatory T cells: role in autoimmune disease and therapeutic opportunities. Immunol. Rev. 223:371–90 [Google Scholar]
  26. Bluestone JA, Buckner JH, Fitch M, Gitelman SE, Gupta S. 26.  et al. 2015. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Sci. Transl. Med. 7:315ra189 [Google Scholar]
  27. Putnam AL, Safinia N, Medvec A, Laszkowska M, Wray M. 27.  et al. 2013. Clinical grade manufacturing of human alloantigen-reactive regulatory T cells for use in transplantation. Am. J. Transplant. 13:3010–20 [Google Scholar]
  28. Tang Q, Bluestone JA. 28.  2013. Regulatory T-cell therapy in transplantation: moving to the clinic. Cold Spring Harb. Perspect. Med. 3:a015552 [Google Scholar]
  29. Bailey AM, Arcidiacono J, Benton KA, Taraporewala Z, Winitsky S. 29.  2015. United States Food and Drug Administration regulation of gene and cell therapies. Adv. Exp. Med. Biol 8711–29 [Google Scholar]
  30. Downing NS, Aminawung JA, Shah ND, Krumholz HM, Ross JS. 30.  2014. Clinical trial evidence supporting FDA approval of novel therapeutic agents, 2005–2012. JAMA 311:368–77 [Google Scholar]
  31. Harvath L. 31.  2009. A brief history of US FDA regulation of human cells and tissues. Cellular Therapy: Principles, Methods, and Regulations EM Areman, K Loper 2–12 Bethesda, MD: AABB [Google Scholar]
  32. Kennett S, Porter C, Bloom E, Wonnacott K. 32.  2009. The FDA perspective on the manufacturing, production, and processing of regulated cellular therapies. In Cellular Therapy: Principles, Methods, and Regulations, ed. EM Areman, K Loper, pp. 18–25. Bethesda, MD: AABB
  33. 33. US Dep. Health Hum. Serv., Food Drug Adm. 2008. Guidance for Industry: CGMP for Phase 1 Investigational Drugs Rockville, MD: FDA http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm070273.pdf [Google Scholar]
  34. Au P, Hursh DA, Lim A, Moos MC Jr., Oh SS. 34.  et al. 2012. FDA oversight of cell therapy clinical trials. Sci. Transl. Med. 4:149fs31 [Google Scholar]
  35. Chambers RW, Foley HT, Schmidt PJ. 35.  1969. Transmission of syphilis by fresh blood components. Transfusion 9:32–34 [Google Scholar]
  36. Orton S. 36.  2001. Syphilis and blood donors: what we know, what we do not know, and what we need to know. Transfus. Med. Rev 15282–91 [Google Scholar]
  37. Gee AP. 37.  1999. Product release assays. Cytotherapy 1:485–91 [Google Scholar]
  38. 38. US Dep. Health Hum. Serv., Food Drug Adm. 2011. Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products Rockville, MD: FDA http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/CellularandGeneTherapy/UCM243392.pdf [Google Scholar]
  39. 39. US Dep. Health Hum. Serv., Cent. Medicare & Medicaid Serv. 2011. Clinical Laboratory Improvement Amendments of 1988 (CLIA)—CLIA Applicability for Laboratory Testing Associated with Blood, Cells/Tissue, and Organs Baltimore, MD: CMS https://www.cms.gov/Medicare/Provider-Enrollment-and-Certification/SurveyCertificationGenInfo/Downloads/SCLetter11_08.pdf [Google Scholar]
  40. Osborn MJ, Webber BR, Knipping F, Lonetree CL, Tennis N. 40.  et al. 2016. Evaluation of TCR gene editing achieved by TALENs, CRISPR/Cas9, and megaTAL nucleases. Mol. Ther. 24:570–81 [Google Scholar]
  41. Gaj T, Gersbach CA, Barbas CF III. 41.  2013. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol 31:397–405 [Google Scholar]
  42. Kim H, Kim JS. 42.  2014. A guide to genome engineering with programmable nucleases. Nat. Rev. Genet. 15:321–34 [Google Scholar]
  43. Osborn MJ, Tolar J. 43.  2016. Cellular engineering and disease modeling with gene-editing nucleases. Genome Editing: The Next Step in Gene Therapy T Cathomen, M Hirsch, M Porteus 223–58 New York: Springer [Google Scholar]
  44. Yuan J, Wang J, Crain K, Fearns C, Kim KA. 44.  et al. 2012. Zinc-finger nuclease editing of human cxcr4 promotes HIV-1 CD4+ T cell resistance and enrichment. Mol. Ther. 20:849–59 [Google Scholar]
  45. Santiago Y, Chan E, Liu PQ, Orlando S, Zhang L. 45.  et al. 2008. Targeted gene knockout in mammalian cells by using engineered zinc-finger nucleases. PNAS 105:5809–14 [Google Scholar]
  46. Davis L, Maizels N. 46.  2011. DNA nicks promote efficient and safe targeted gene correction. PLOS ONE 6:e23981 [Google Scholar]
  47. Schumann K, Lin S, Boyer E, Simeonov DR, Subramaniam M. 47.  et al. 2015. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins. PNAS 112:10437–42 [Google Scholar]
  48. Provasi E, Genovese P, Lombardo A, Magnani Z, Liu PQ. 48.  et al. 2012. Editing T cell specificity towards leukemia by zinc finger nucleases and lentiviral gene transfer. Nat. Med. 18:807–15 [Google Scholar]
  49. Wang J, DeClercq JJ, Hayward SB, Li PW, Shivak DA. 49.  et al. 2016. Highly efficient homology-driven genome editing in human T cells by combining zinc-finger nuclease mRNA and AAV6 donor delivery. Nucleic Acids Res 44:e30 [Google Scholar]
  50. Szczepek M, Brondani V, Buchel J, Serrano L, Segal DJ, Cathomen T. 50.  2007. Structure-based redesign of the dimerization interface reduces the toxicity of zinc-finger nucleases. Nat. Biotechnol. 25:786–93 [Google Scholar]
  51. Cornu TI, Thibodeau-Beganny S, Guhl E, Alwin S, Eichtinger M. 51.  et al. 2008. DNA-binding specificity is a major determinant of the activity and toxicity of zinc-finger nucleases. Mol. Ther. 16:352–58 [Google Scholar]
  52. Ousterout DG, Gersbach CA. 52.  2016. The development of TALE nucleases for biotechnology. Methods Mol. Biol. 1338:27–42 [Google Scholar]
  53. Moscou MJ, Bogdanove AJ. 53.  2009. A simple cipher governs DNA recognition by TAL effectors. Science 326:1501 [Google Scholar]
  54. Boch J, Scholze H, Schornack S, Landgraf A, Hahn S. 54.  et al. 2009. Breaking the code of DNA binding specificity of TAL-type III effectors. Science 326:1509–12 [Google Scholar]
  55. Holkers M, Maggio I, Liu J, Janssen JM, Miselli F. 55.  et al. 2013. Differential integrity of TALE nuclease genes following adenoviral and lentiviral vector gene transfer into human cells. Nucleic Acids Res 41:e63 [Google Scholar]
  56. Valton J, Guyot V, Marechal A, Filhol JM, Juillerat A. 56.  et al. 2015. A multidrug-resistant engineered CAR T cell for allogeneic combination immunotherapy. Mol. Ther. 23:1507–18 [Google Scholar]
  57. Berdien B, Mock U, Atanackovic D, Fehse B. 57.  2014. TALEN-mediated editing of endogenous T-cell receptors facilitates efficient reprogramming of T lymphocytes by lentiviral gene transfer. Gene Ther 21:539–48 [Google Scholar]
  58. Menger L, Gouble A, Marzolini MA, Pachnio A, Bergerhoff K. 58.  et al. 2015. TALEN-mediated genetic inactivation of the glucocorticoid receptor in cytomegalovirus-specific T cells. Blood 126:2781–89 [Google Scholar]
  59. Boissel S, Jarjour J, Astrakhan A, Adey A, Gouble A. 59.  et al. 2014. MegaTALs: a rare-cleaving nuclease architecture for therapeutic genome engineering. Nucleic Acids Res 42:2591–601 [Google Scholar]
  60. Smith J, Grizot S, Arnould S, Duclert A, Epinat JC. 60.  et al. 2006. A combinatorial approach to create artificial homing endonucleases cleaving chosen sequences. Nucleic Acids Res 34:e149 [Google Scholar]
  61. Fu Y, Foden JA, Khayter C, Maeder ML, Reyon D. 61.  et al. 2013. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat. Biotechnol. 31:822–26 [Google Scholar]
  62. Slaymaker IM, Gao L, Zetsche B, Scott DA, Yan WX, Zhang F. 62.  2016. Rationally engineered Cas9 nucleases with improved specificity. Science 351:84–88 [Google Scholar]
  63. Hou P, Chen S, Wang S, Yu X, Chen Y. 63.  et al. 2015. Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection. Sci. Rep. 5:15577 [Google Scholar]
  64. Kaminski R, Chen Y, Fischer T, Tedaldi E, Napoli A. 64.  et al. 2016. Elimination of HIV-1 genomes from human T-lymphoid cells by CRISPR/Cas9 gene editing. Sci. Rep. 6:22555 [Google Scholar]
  65. Suerth JD, Schambach A, Baum C. 65.  2012. Genetic modification of lymphocytes by retrovirus-based vectors. Curr. Opin. Immunol. 24:598–608 [Google Scholar]
  66. Hacein-Bey-Abina S, Garrigue A, Wang GP, Soulier J, Lim A. 66.  et al. 2008. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J. Clin. Investig. 118:3132–42 [Google Scholar]
  67. Geng X, Doitsh G, Yang Z, Galloway NL, Greene WC. 67.  2014. Efficient delivery of lentiviral vectors into resting human CD4 T cells. Gene Ther 21:444–49 [Google Scholar]
  68. Frecha C, Levy C, Costa C, Negre D, Amirache F. 68.  et al. 2011. Measles virus glycoprotein-pseudotyped lentiviral vector-mediated gene transfer into quiescent lymphocytes requires binding to both SLAM and CD46 entry receptors. J. Virol. 85:5975–85 [Google Scholar]
  69. Modlich U, Navarro S, Zychlinski D, Maetzig T, Knoess S. 69.  et al. 2009. Insertional transformation of hematopoietic cells by self-inactivating lentiviral and gammaretroviral vectors. Mol. Ther. 17:1919–28 [Google Scholar]
  70. Singh H, Huls H, Kebriaei P, Cooper LJ. 70.  2014. A new approach to gene therapy using Sleeping Beauty to genetically modify clinical-grade T cells to target CD19. Immunol. Rev. 257:181–90 [Google Scholar]
  71. Singh H, Figliola MJ, Dawson MJ, Olivares S, Zhang L. 71.  et al. 2013. Manufacture of clinical-grade CD19-specific T cells stably expressing chimeric antigen receptor using Sleeping Beauty system and artificial antigen presenting cells. PLOS ONE 8:e64138 [Google Scholar]
  72. Field AC, Vink C, Gabriel R, Al-Subki R, Schmidt M. 72.  et al. 2013. Comparison of lentiviral and Sleeping Beauty mediated αβ T cell receptor gene transfer. PLOS ONE 8:e68201 [Google Scholar]
  73. Turchiano G, Latella MC, Gogol-Doring A, Cattoglio C, Mavilio F. 73.  et al. 2014. Genomic analysis of Sleeping Beauty transposon integration in human somatic cells. PLOS ONE 9:e112712 [Google Scholar]
  74. Manuri PV, Wilson MH, Maiti SN, Mi T, Singh H. 74.  et al. 2010. piggyBac transposon/transposase system to generate CD19-specific T cells for the treatment of B-lineage malignancies. Hum. Gene Ther. 21:427–37 [Google Scholar]
  75. Galvan DL, Nakazawa Y, Kaja A, Kettlun C, Cooper LJ. 75.  et al. 2009. Genome-wide mapping of PiggyBac transposon integrations in primary human T cells. J. Immunother. 32:837–44 [Google Scholar]
  76. Beatty GL, Haas AR, Maus MV, Torigian DA, Soulen MC. 76.  et al. 2014. Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol. Res. 2:112–20 [Google Scholar]
  77. Holling TM, van der Stoep N, Quinten E, van den Elsen PJ. 77.  2002. Activated human T cells accomplish MHC class II expression through T cell-specific occupation of class II transactivator promoter III. J. Immunol. 168:763–70 [Google Scholar]
  78. Gragert L, Eapen M, Williams E, Freeman J, Spellman S. 78.  et al. 2014. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N. Engl. J. Med. 371:339–48 [Google Scholar]
  79. Heddle NM, Soutar RL, O'Hoski PL, Singer J, McBride JA. 79.  et al. 1995. A prospective study to determine the frequency and clinical significance of alloimmunization post-transfusion. Br. J. Haematol. 91:1000–5 [Google Scholar]
  80. Davis JL, Theoret MR, Zheng Z, Lamers CH, Rosenberg SA, Morgan RA. 80.  2010. Development of human anti-murine T-cell receptor antibodies in both responding and nonresponding patients enrolled in TCR gene therapy trials. Clin. Cancer Res. 16:5852–61 [Google Scholar]
  81. Jensen MC, Popplewell L, Cooper LJ, DiGiusto D, Kalos M. 81.  et al. 2010. Antitransgene rejection responses contribute to attenuated persistence of adoptively transferred CD20/CD19-specific chimeric antigen receptor redirected T cells in humans. Biol. Blood Marrow Transplant. 16:1245–56 [Google Scholar]
  82. Heeger PS. 82.  2003. T-cell allorecognition and transplant rejection: a summary and update. Am. J. Transplant. 3:525–33 [Google Scholar]
  83. Wagner FF, Flegel WA. 83.  1995. Transfusion-associated graft-versus-host disease: risk due to homozygous HLA haplotypes. Transfusion 35:284–91 [Google Scholar]
  84. Takahashi K, Juji T, Miyamoto M, Uchida S, Akaza T. 84.  et al. 1994. Analysis of risk factors for post-transfusion graft-versus-host disease in Japan. Japanese Red Cross PT-GVHD Study Group. Lancet 343:700–2 [Google Scholar]
  85. Lee TH, Paglieroni T, Ohto H, Holland PV, Busch MP. 85.  1999. Survival of donor leukocyte subpopulations in immunocompetent transfusion recipients: frequent long-term microchimerism in severe trauma patients. Blood 93:3127–39 [Google Scholar]
  86. Reed W, Lee TH, Norris PJ, Utter GH, Busch MP. 86.  2007. Transfusion-associated microchimerism: a new complication of blood transfusions in severely injured patients. Semin. Hematol. 44:24–31 [Google Scholar]
  87. Utter GH, Owings JT, Lee TH, Paglieroni TG, Reed WF. 87.  et al. 2004. Blood transfusion is associated with donor leukocyte microchimerism in trauma patients. J. Trauma 57:702–7; discussion 7–8 [Google Scholar]
  88. Lee TH, Paglieroni T, Utter GH, Chafets D, Gosselin RC. 88.  et al. 2005. High-level long-term white blood cell microchimerism after transfusion of leukoreduced blood components to patients resuscitated after severe traumatic injury. Transfusion 45:1280–90 [Google Scholar]
  89. Poirot L, Philip B, Schiffer-Mannioui C, Le Clerre D, Chion-Sotinel I. 89.  et al. 2015. Multiplex genome-edited T-cell manufacturing platform for “off-the-shelf” adoptive T-cell immunotherapies. Cancer Res 75:3853–64 [Google Scholar]
  90. Scarisbrick JJ, Dignan FL, Tulpule S, Gupta ED, Kolade S. 90.  et al. 2015. A multicentre UK study of GVHD following DLI: Rates of GVHD are high but mortality from GVHD is infrequent. Bone Marrow Transplant 50:62–67 [Google Scholar]
  91. Cruz CR, Micklethwaite KP, Savoldo B, Ramos CA, Lam S. 91.  et al. 2013. Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study. Blood 122:2965–73 [Google Scholar]
  92. Gerdemann U, Katari UL, Papadopoulou A, Keirnan JM, Craddock JA. 92.  et al. 2013. Safety and clinical efficacy of rapidly-generated trivirus-directed T cells as treatment for adenovirus, EBV, and CMV infections after allogeneic hematopoietic stem cell transplant. Mol. Ther. 21:2113–21 [Google Scholar]
  93. Papadopoulou A, Gerdemann U, Katari UL, Tzannou I, Liu H. 93.  et al. 2014. Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. Sci. Transl. Med. 6:242ra83 [Google Scholar]
  94. Papadopoulos EB, Ladanyi M, Emanuel D, Mackinnon S, Boulad F. 94.  et al. 1994. Infusions of donor leukocytes to treat Epstein-Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation. N. Engl. J. Med. 330:1185–91 [Google Scholar]
  95. Haque T, Wilkie GM, Jones MM, Higgins CD, Urquhart G. 95.  et al. 2007. Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial. Blood 110:1123–31 [Google Scholar]
  96. Leen AM, Bollard CM, Mendizabal AM, Shpall EJ, Szabolcs P. 96.  et al. 2013. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood 121:5113–23 [Google Scholar]
  97. Themeli M, Kloss CC, Ciriello G, Fedorov VD, Perna F. 97.  et al. 2013. Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy. Nat. Biotechnol. 31:928–33 [Google Scholar]
  98. Vizcardo R, Masuda K, Yamada D, Ikawa T, Shimizu K. 98.  et al. 2013. Regeneration of human tumor antigen-specific T cells from iPSCs derived from mature CD8+ T cells. Cell Stem Cell 12:31–36 [Google Scholar]
  99. Nishimura T, Kaneko S, Kawana-Tachikawa A, Tajima Y, Goto H. 99.  et al. 2013. Generation of rejuvenated antigen-specific T cells by reprogramming to pluripotency and redifferentiation. Cell Stem Cell 12:114–26 [Google Scholar]
  100. Torikai H, Reik A, Soldner F, Warren EH, Yuen C. 100.  et al. 2013. Toward eliminating HLA class I expression to generate universal cells from allogeneic donors. Blood 122:1341–49 [Google Scholar]
  101. Torikai H, Reik A, Liu PQ, Zhou Y, Zhang L. 101.  et al. 2012. 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 119:5697–705 [Google Scholar]
  102. Riteau B, Menier C, Khalil-Daher I, Martinozzi S, Pla M. 102.  et al. 2001. HLA-G1 co-expression boosts the HLA class I-mediated NK lysis inhibition. Int. Immunol. 13:193–201 [Google Scholar]
  103. Rouas-Freiss N, Marchal RE, Kirszenbaum M, Dausset J, Carosella ED. 103.  1997. The α1 domain of HLA-G1 and HLA-G2 inhibits cytotoxicity induced by natural killer cells: Is HLA-G the public ligand for natural killer cell inhibitory receptors?. PNAS 94:5249–54 [Google Scholar]
  104. Qasim W, Amrolia PJ, Samarasinghe S, Zhan H, Stafford S. 104.  et al. 2015. First clinical application of Talen engineered universal CAR19 T cells in B-ALL. Blood 126:2046 [Google Scholar]
  105. Way JC, Collins JJ, Keasling JD, Silver PA. 105.  2014. Integrating biological redesign: where synthetic biology came from and where it needs to go. Cell 157:151–61 [Google Scholar]
  106. Kwok R. 106.  2010. Five hard truths for synthetic biology. Nature 463:288–90 [Google Scholar]
  107. Silver PA, Way JC, Arnold FH, Meyerowitz JT. 107.  2014. Synthetic biology: engineering explored. Nature 509:166–67 [Google Scholar]
  108. Dotti G, Gottschalk S, Savoldo B, Brenner MK. 108.  2014. Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol. Rev. 257:107–26 [Google Scholar]
  109. Kloss CC, Condomines M, Cartellieri M, Bachmann M, Sadelain M. 109.  2013. Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Nat. Biotechnol. 31:71–75 [Google Scholar]
  110. Wilkie S, van Schalkwyk MC, Hobbs S, Davies DM, van der Stegen SJ. 110.  et al. 2012. Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling. J. Clin. Immunol. 32:1059–70 [Google Scholar]
  111. Fedorov VD, Themeli M, Sadelain M. 111.  2013. PD-1- and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci. Transl. Med. 5:215ra172 [Google Scholar]
  112. Morsut L, Roybal KT, Xiong X, Gordley RM, Coyle SM. 112.  et al. 2016. Engineering customized cell sensing and response behaviors using synthetic notch receptors. Cell 164:780–91 [Google Scholar]
  113. Roybal KT, Rupp LJ, Morsut L, Walker WJ, McNally KA. 113.  et al. 2016. Precision tumor recognition by T cells with combinatorial antigen-sensing circuits. Cell 164:770–79 [Google Scholar]
  114. Conklin BR, Hsiao EC, Claeysen S, Dumuis A, Srinivasan S. 114.  et al. 2008. Engineering GPCR signaling pathways with RASSLs. Nat. Methods 5:673–78 [Google Scholar]
  115. Park JS, Rhau B, Hermann A, McNally KA, Zhou C. 115.  et al. 2014. Synthetic control of mammalian-cell motility by engineering chemotaxis to an orthogonal bioinert chemical signal. PNAS 111:5896–901 [Google Scholar]
  116. Townshend B, Kennedy AB, Xiang JS, Smolke CD. 116.  2015. High-throughput cellular RNA device engineering. Nat. Methods 12:989–94 [Google Scholar]
  117. Chen YY, Jensen MC, Smolke CD. 117.  2010. Genetic control of mammalian T-cell proliferation with synthetic RNA regulatory systems. PNAS 107:8531–36 [Google Scholar]
  118. Wu CY, Roybal KT, Puchner EM, Onuffer J, Lim WA. 118.  2015. Remote control of therapeutic T cells through a small molecule–gated chimeric receptor. Science 350:aab4077 [Google Scholar]
  119. Ma JS, Kim JY, Kazane SA, Choi SH, Yun HY. 119.  et al. 2016. Versatile strategy for controlling the specificity and activity of engineered T cells. PNAS 113:E450–58 [Google Scholar]
  120. Rodgers DT, Mazagova M, Hampton EN, Cao Y, Ramadoss NS. 120.  et al. 2016. Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies. PNAS 113:E459–68 [Google Scholar]
  121. Tamada K, Geng D, Sakoda Y, Bansal N, Srivastava R. 121.  et al. 2012. Redirecting gene-modified T cells toward various cancer types using tagged antibodies. Clin. Cancer Res. 18:6436–45 [Google Scholar]
  122. Urbanska K, Lanitis E, Poussin M, Lynn RC, Gavin BP. 122.  et al. 2012. A universal strategy for adoptive immunotherapy of cancer through use of a novel T-cell antigen receptor. Cancer Res 72:1844–52 [Google Scholar]
  123. Weissinger EM, Borchers S, Silvani A, Provasi E, Radrizzani M. 123.  et al. 2015. Long term follow up of patients after allogeneic stem cell transplantation and transfusion of HSV-TK transduced T-cells. Front. Pharmacol. 6:76 [Google Scholar]
  124. Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. 124.  2010. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol. Ther. 18:843–51 [Google Scholar]
  125. Morgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF. 125.  et al. 2013. Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J. Immunother. 36:133–51 [Google Scholar]
  126. Linette GP, Stadtmauer EA, Maus MV, Rapoport AP, Levine BL. 126.  et al. 2013. Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood 122:863–71 [Google Scholar]
  127. Lamers CH, Sleijfer S, van Steenbergen S, van Elzakker P, van Krimpen B. 127.  et al. 2013. Treatment of metastatic renal cell carcinoma with CAIX CAR-engineered T cells: clinical evaluation and management of on-target toxicity. Mol. Ther. 21:904–12 [Google Scholar]
  128. Parkhurst MR, Yang JC, Langan RC, Dudley ME, Nathan DA. 128.  et al. 2011. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol. Ther. 19:620–26 [Google Scholar]
  129. Davila ML, Riviere I, Wang X, Bartido S, Park J. 129.  et al. 2014. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci. Transl. Med. 6:224ra25 [Google Scholar]
  130. Kochenderfer JN, Dudley ME, Feldman SA, Wilson WH, Spaner DE. 130.  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 119:2709–20 [Google Scholar]
  131. Gross G, Eshhar Z. 131.  2016. Therapeutic potential of T cell chimeric antigen receptors (CARs) in cancer treatment: counteracting off-tumor toxicities for safe CAR T cell therapy. Annu. Rev. Pharmacol. Toxicol. 56:59–83 [Google Scholar]
  132. Tey SK, Dotti G, Rooney CM, Heslop HE, Brenner MK. 132.  2007. Inducible caspase 9 suicide gene to improve the safety of allodepleted T cells after haploidentical stem cell transplantation. Biol. Blood Marrow Transplant. 13:913–24 [Google Scholar]
  133. Di Stasi A, Tey SK, Dotti G, Fujita Y, Kennedy-Nasser A. 133.  et al. 2011. Inducible apoptosis as a safety switch for adoptive cell therapy. N. Engl. J. Med. 365:1673–83 [Google Scholar]
  134. Budde LE, Berger C, Lin Y, Wang J, Lin X. 134.  et al. 2013. Combining a CD20 chimeric antigen receptor and an inducible caspase 9 suicide switch to improve the efficacy and safety of T cell adoptive immunotherapy for lymphoma. PLOS ONE 8:e82742 [Google Scholar]
  135. Zhou X, Di Stasi A, Tey SK, Krance RA, Martinez C. 135.  et al. 2014. Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene. Blood 123:3895–905 [Google Scholar]
  136. Spencer DM, Belshaw PJ, Chen L, Ho SN, Randazzo F. 136.  et al. 1996. Functional analysis of Fas signaling in vivo using synthetic inducers of dimerization. Curr. Biol. 6:839–47 [Google Scholar]
  137. Belshaw PJ, Spencer DM, Crabtree GR, Schreiber SL. 137.  1996. Controlling programmed cell death with a cyclophilin-cyclosporin-based chemical inducer of dimerization. Chem. Biol. 3:731–38 [Google Scholar]
  138. Thomis DC, Marktel S, Bonini C, Traversari C, Gilman M. 138.  et al. 2001. A Fas-based suicide switch in human T cells for the treatment of graft-versus-host disease. Blood 97:1249–57 [Google Scholar]
  139. Bonini C, Ferrari G, Verzeletti S, Servida P, Zappone E. 139.  et al. 1997. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 276:1719–24 [Google Scholar]
  140. Berger C, Flowers ME, Warren EH, Riddell SR. 140.  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 107:2294–302 [Google Scholar]
  141. Mercier-Letondal P, Deschamps M, Sauce D, Certoux JM, Milpied N. 141.  et al. 2008. Early immune response against retrovirally transduced herpes simplex virus thymidine kinase-expressing gene-modified T cells coinfused with a T cell-depleted marrow graft: an altered immune response?. Hum. Gene Ther. 19:937–50 [Google Scholar]
  142. Philip B, Kokalaki E, Mekkaoui L, Thomas S, Straathof K. 142.  et al. 2014. A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy. Blood 124:1277–87 [Google Scholar]
  143. Griffioen M, van Egmond EH, Kester MG, Willemze R, Falkenburg JH, Heemskerk MH. 143.  2009. Retroviral transfer of human CD20 as a suicide gene for adoptive T-cell therapy. Haematologica 94:1316–20 [Google Scholar]
  144. Kieback E, Charo J, Sommermeyer D, Blankenstein T, Uckert W. 144.  2008. A safeguard eliminates T cell receptor gene-modified autoreactive T cells after adoptive transfer. PNAS 105:623–28 [Google Scholar]
  145. Wang X, Chang WC, Wong CW, Colcher D, Sherman M. 145.  et al. 2011. A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood 118:1255–63 [Google Scholar]
  146. Zhao Y, Zheng Z, Cohen CJ, Gattinoni L, Palmer DC. 146.  et al. 2006. High-efficiency transfection of primary human and mouse T lymphocytes using RNA electroporation. Mol. Ther. 13:151–59 [Google Scholar]
  147. Wu C-Y, Roybal KT, Puchner EM, Onuffer J, Lim WA. 147.  2015. Remote control of therapeutic T cells through a small molecule–gated chimeric receptor. Science 350:aab4077 [Google Scholar]
  148. Fischbach MA, Bluestone JA, Lim WA. 148.  2013. Cell-based therapeutics: the next pillar of medicine. Sci. Transl. Med. 5:179ps7 [Google Scholar]
/content/journals/10.1146/annurev-pathol-052016-100304
Loading
/content/journals/10.1146/annurev-pathol-052016-100304
Loading

Data & Media loading...

  • Article Type: Review Article
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