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Annual Review of Biomedical Engineering

Volume 23, 2021

In Situ Programming of CAR T Cells

Abstract

Gene therapy makes it possible to engineer chimeric antigen receptors (CARs) to create T cells that target specific diseases. However, current approaches require elaborate and expensive protocols to manufacture engineered T cells ex vivo, putting this therapy beyond the reach of many patients who might benefit. A solution could be to program T cells in vivo. Here, we evaluate the clinical need for in situ CAR T cell programming, compare competing technologies, review current progress, and provide a perspective on the long-term impact of this emerging and rapidly flourishing biotechnology field.

Keyword(s): CAR T cell therapy, gene therapy, nanoparticle, off-the-shelf T cell therapy
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2021-07-13
2024-04-28
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Literature Cited

  1. 1. 
    Park JH, Riviere I, Gonen M, Wang X, Senechal B et al. 2018. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N. Engl. J. Med. 378:449–59
     [Google Scholar]
  2. 2. 
    Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S et al. 2019. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N. Engl. J. Med. 380:1726–37
     [Google Scholar]
  3. 3. 
    Chapuis AG, Egan DN, Bar M, Schmitt TM, McAfee MS et al. 2019. T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant. Nat. Med. 25:1064–72
     [Google Scholar]
  4. 4. 
    Fry TJ, Shah NN, Orentas RJ, Stetler-Stevenson M, Yuan CM et al. 2018. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat. Med. 24:20–28
     [Google Scholar]
  5. 5. 
    Rockoff JD. 2018. The million-dollar cancer treatment: Who will pay?. Wall Street J. Apr 26: https://www.wsj.com/articles/the-million-dollar-cancer-treatment-no-one-knows-how-to-pay-for-1524740401
    [Google Scholar]
  6. 6. 
    Roddie C, O'Reilly M, Dias Alves Pinto J, Vispute K, Lowdell M 2019. Manufacturing chimeric antigen receptor T cells: issues and challenges. Cytotherapy 21:327–40
     [Google Scholar]
  7. 7. 
    Gomes-Silva D, Ramos CA. 2018. Cancer immunotherapy using CAR-T cells: from the research bench to the assembly line. Biotechnol. J. 13:1700097
     [Google Scholar]
  8. 8. 
    Sheikh NA, Petrylak D, Kantoff PW, Dela Rosa C, Stewart FP et al. 2013. Sipuleucel-T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancer. Cancer Immunol. Immunother. 62:137–47
     [Google Scholar]
  9. 9. 
    Kantoff PW, Schuetz TJ, Blumenstein BA, Glode LM, Bilhartz DL et al. 2010. Overall survival analysis of a phase II randomized controlled trial of a poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J. Clin. Oncol. 28:1099–105
     [Google Scholar]
  10. 10. 
    Zussman BM, Engh JA. 2015. Outcomes of the ACT III study: rindopepimut (CDX-110) therapy for glioblastoma. Neurosurgery 76:N17
     [Google Scholar]
  11. 11. 
    Leveque D, Wisniewski S, Jehl F. 2005. Pharmacokinetics of therapeutic monoclonal antibodies used in oncology. Anticancer Res 25:2327–43
     [Google Scholar]
  12. 12. 
    Thurber GM, Schmidt MM, Wittrup KD. 2008. Antibody tumor penetration: transport opposed by systemic and antigen-mediated clearance. Adv. Drug Deliv. Rev. 60:1421–34
     [Google Scholar]
  13. 13. 
    Suryadevara CM, Gedeon PC, Sanchez-Perez L, Verla T, Alvarez-Breckenridge C et al. 2015. Are BiTEs the “missing link” in cancer therapy?. Oncoimmunology 4:e1008339
     [Google Scholar]
  14. 14. 
    Sung JA, Pickeral J, Liu L, Stanfield-Oakley SA, Lam CY et al. 2015. Dual-affinity re-targeting proteins direct T cell-mediated cytolysis of latently HIV-infected cells. J. Clin. Investig. 125:4077–90
     [Google Scholar]
  15. 15. 
    Fan D, Li W, Yang Y, Zhang X, Zhang Q et al. 2015. Redirection of CD4+ and CD8+ T lymphocytes via an anti-CD3 × anti-CD19 bi-specific antibody combined with cytosine arabinoside and the efficient lysis of patient-derived B-ALL cells. J. Hematol. Oncol. 8:108
     [Google Scholar]
  16. 16. 
    Topp MS, Gokbuget N, Stein AS, Zugmaier G, O'Brien S et al. 2015. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol 16:57–66
     [Google Scholar]
  17. 17. 
    Am. Cancer Soc 2015. Cancer facts & figures 2015 Annu. Rep., Am. Cancer Soc Atlanta: https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2015.html
  18. 18. 
    Rosenberg SA. 2011. Cell transfer immunotherapy for metastatic solid cancer—what clinicians need to know. Nat. Rev. Clin. Oncol. 8:577–85
     [Google Scholar]
  19. 19. 
    Tumeh PC, Koya RC, Chodon T, Graham NA, Graeber TG et al. 2010. The impact of ex vivo clinical grade activation protocols on human T-cell phenotype and function for the generation of genetically modified cells for adoptive cell transfer therapy. J. Immunother. 33:759–68
     [Google Scholar]
  20. 20. 
    Riker A, Cormier J, Panelli M, Kammula U, Wang E et al. 1999. Immune selection after antigen-specific immunotherapy of melanoma. Surgery 126:112–20
     [Google Scholar]
  21. 21. 
    Somasundaram R, Herlyn M. 2013. Relapse of melanoma after successful adoptive T-cell therapy: escape through inflammation-induced phenotypic melanoma cell plasticity. Pigment Cell Melanoma Res 26:2–4
     [Google Scholar]
  22. 22. 
    Kaluza KM, Thompson JM, Kottke TJ, Flynn Gilmer HC, Knutson DL, Vile RG 2012. Adoptive T cell therapy promotes the emergence of genomically altered tumor escape variants. Int. J. Cancer. 131:844–54
     [Google Scholar]
  23. 23. 
    Frimpong K, Spector SA. 2000. Cotransduction of nondividing cells using lentiviral vectors. Gene Ther 7:1562–69
     [Google Scholar]
  24. 24. 
    Breckpot K, Escors D, Arce F, Lopes L, Karwacz K et al. 2010. HIV-1 lentiviral vector immunogenicity is mediated by Toll-like receptor 3 (TLR3) and TLR7. J. Virol. 84:5627–36
     [Google Scholar]
  25. 25. 
    DePolo NJ, Reed JD, Sheridan PL, Townsend K, Sauter SL et al. 2000. VSV-G pseudotyped lentiviral vector particles produced in human cells are inactivated by human serum. Mol. Ther. 2:218–22
     [Google Scholar]
  26. 26. 
    White M, Whittaker R, Gandara C, Stoll EA. 2017. A guide to approaching regulatory considerations for lentiviral-mediated gene therapies. Hum. Gene Ther. Methods 28:163–76
     [Google Scholar]
  27. 27. 
    Frecha C, Szecsi J, Cosset FL, Verhoeyen E. 2008. Strategies for targeting lentiviral vectors. Curr. Gene Ther. 8:449–60
     [Google Scholar]
  28. 28. 
    Jamali A, Kapitza L, Schaser T, Johnston ICD, Buchholz CJ, Hartmann J. 2019. Highly efficient and selective CAR-gene transfer using CD4- and CD8-targeted lentiviral vectors. Mol. Ther. Methods Clin. Dev. 13:371–79
     [Google Scholar]
  29. 29. 
    Zhou Q, Uhlig KM, Muth A, Kimpel J, Levy C et al. 2015. Exclusive transduction of human CD4+ T cells upon systemic delivery of CD4-targeted lentiviral vectors. J. Immunol. 195:2493–501
     [Google Scholar]
  30. 30. 
    Agarwal S, Weidner T, Thalheimer FB, Buchholz CJ. 2019. In vivo generated human CAR T cells eradicate tumor cells. Oncoimmunology 8:e1671761
     [Google Scholar]
  31. 31. 
    Pfeiffer A, Thalheimer FB, Hartmann S, Frank AM, Bender RR et al. 2018. In vivo generation of human CD19-CAR T cells results in B-cell depletion and signs of cytokine release syndrome. EMBO Mol. Med. 10:e9158
     [Google Scholar]
  32. 32. 
    Milone MC, O'Doherty U. 2018. Clinical use of lentiviral vectors. Leukemia 32:1529–41
     [Google Scholar]
  33. 33. 
    Lana MG, Strauss BE. 2020. Production of lentivirus for the establishment of CAR-T cells. Methods Mol. Biol. 2086:61–67
     [Google Scholar]
  34. 34. 
    Yuan W, Chen J, Cao Y, Yang L, Shen L et al. 2018. Comparative analysis and optimization of protocols for producing recombinant lentivirus carrying the anti-Her2 chimeric antigen receptor gene. J. Gene Med. 20:e3027
     [Google Scholar]
  35. 35. 
    Bauler M, Roberts JK, Wu CC, Fan B, Ferrara F et al. 2020. Production of lentiviral vectors using suspension cells grown in serum-free media. Mol. Ther. Methods Clin. Dev. 17:58–68
     [Google Scholar]
  36. 36. 
    Ellison SM, Liao A, Wood S, Taylor J, Youshani AS et al. 2019. Pre-clinical safety and efficacy of lentiviral vector-mediated ex vivo stem cell gene therapy for the treatment of mucopolysaccharidosis IIIA. Mol. Ther. Methods Clin. Dev. 13:399–413
     [Google Scholar]
  37. 37. 
    White JM, Whittaker GR. 2016. Fusion of enveloped viruses in endosomes. Traffic 17:593–614
     [Google Scholar]
  38. 38. 
    McCarron A, Donnelley M, McIntyre C, Parsons D. 2016. Challenges of up-scaling lentivirus production and processing. J. Biotechnol. 240:23–30
     [Google Scholar]
  39. 39. 
    Modlich U, Navarro S, Zychlinski D, Maetzig T, Knoess S et al. 2009. Insertional transformation of hematopoietic cells by self-inactivating lentiviral and gammaretroviral vectors. Mol. Ther. 17:1919–28
     [Google Scholar]
  40. 40. 
    Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N et al. 2003. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 302:415–19
     [Google Scholar]
  41. 41. 
    Braun CJ, Boztug K, Paruzynski A, Witzel M, Schwarzer A et al. 2014. Gene therapy for Wiskott-Aldrich syndrome—long-term efficacy and genotoxicity. Sci. Transl. Med. 6:227ra33
     [Google Scholar]
  42. 42. 
    Biasco L, Scala S, Basso Ricci L, Dionisio F, Baricordi C et al. 2015. In vivo tracking of T cells in humans unveils decade-long survival and activity of genetically modified T memory stem cells. Sci. Transl. Med. 7:273ra13
     [Google Scholar]
  43. 43. 
    Anguela XM, High KA. 2019. Entering the modern era of gene therapy. Annu. Rev. Med. 70:273–88
     [Google Scholar]
  44. 44. 
    Thomas JA, Ott DE, Gorelick RJ. 2007. Efficiency of human immunodeficiency virus type 1 postentry infection processes: evidence against disproportionate numbers of defective virions. J. Virol. 81:4367–70
     [Google Scholar]
  45. 45. 
    Ramirez JC. 2018. Lentiviral vectors come of age? Hurdles and challenges in scaling up manufacture. Systems Biology, ed. D Vlachakis 33–44 London: IntechOpen
     [Google Scholar]
  46. 46. 
    Chen HY, Di Mascio M, Perelson AS, Ho DD, Zhang L 2007. Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques. PNAS 104:19079–84
     [Google Scholar]
  47. 47. 
    Zhou Q, Schneider IC, Edes I, Honegger A, Bach P et al. 2012. T-cell receptor gene transfer exclusively to human CD8+ cells enhances tumor cell killing. Blood 120:4334–42
     [Google Scholar]
  48. 48. 
    Annoni A, Goudy K, Akbarpour M, Naldini L, Roncarolo MG. 2013. Immune responses in liver-directed lentiviral gene therapy. Transl. Res. 161:230–40
     [Google Scholar]
  49. 49. 
    Milani M, Annoni A, Bartolaccini S, Biffi M, Russo F et al. 2017. Genome editing for scalable production of alloantigen-free lentiviral vectors for in vivo gene therapy. EMBO Mol. Med. 9:1558–73
     [Google Scholar]
  50. 50. 
    Quarta A, Bernareggi D, Benigni F, Luison E, Nano G et al. 2015. Targeting FR-expressing cells in ovarian cancer with Fab-functionalized nanoparticles: a full study to provide the proof of principle from in vitro to in vivo. Nanoscale 7:2336–51
     [Google Scholar]
  51. 51. 
    Stremitzer S, Berghoff AS, Volz NB, Zhang W, Yang D et al. 2015. Genetic variants associated with colorectal brain metastases susceptibility and survival. Pharmacogenom. J. 17:29–35
     [Google Scholar]
  52. 52. 
    Satpathy M, Zielinski R, Lyakhov I, Yang L 2015. Optical imaging of ovarian cancer using HER-2 affibody conjugated nanoparticles. Methods Mol. Biol. 1219:171–85
     [Google Scholar]
  53. 53. 
    Fahmy TM, Fong PM, Park J, Constable T, Saltzman WM. 2007. Nanosystems for simultaneous imaging and drug delivery to T cells. AAPS J 9:E171–80
     [Google Scholar]
  54. 54. 
    Fahmy TM, Schneck JP, Saltzman WM. 2007. A nanoscopic multivalent antigen-presenting carrier for sensitive detection and drug delivery to T cells. Nanomedicine 3:75–85
     [Google Scholar]
  55. 55. 
    Ramishetti S, Kedmi R, Goldsmith M, Leonard F, Sprague AG et al. 2015. Systemic gene silencing in primary T lymphocytes using targeted lipid nanoparticles. ACS Nano 9:6706–16
     [Google Scholar]
  56. 56. 
    Yang YS, Moynihan KD, Bekdemir A, Dichwalkar TM, Noh MM et al. 2018. Targeting small molecule drugs to T cells with antibody-directed cell-penetrating gold nanoparticles. Biomater. Sci. 7:113–24
     [Google Scholar]
  57. 57. 
    Schmid D, Park CG, Hartl CA, Subedi N, Cartwright AN et al. 2017. T cell-targeting nanoparticles focus delivery of immunotherapy to improve antitumor immunity. Nat. Commun. 8:1747
     [Google Scholar]
  58. 58. 
    Schallon A, Synatschke CV, Jerome V, Muller AH, Freitag R. 2012. Nanoparticulate nonviral agent for the effective delivery of pDNA and siRNA to differentiated cells and primary human T lymphocytes. Biomacromolecules 13:3463–74
     [Google Scholar]
  59. 59. 
    Chen G, Chen W, Wu Z, Yuan R, Li H et al. 2009. MRI-visible polymeric vector bearing CD3 single chain antibody for gene delivery to T cells for immunosuppression. Biomaterials 30:1962–70
     [Google Scholar]
  60. 60. 
    Liu J, Stace-Naughton A, Jiang X, Brinker CJ. 2009. Porous nanoparticle supported lipid bilayers (protocells) as delivery vehicles. J. Am. Chem. Soc. 131:1354–55
     [Google Scholar]
  61. 61. 
    Mangraviti A, Tzeng SY, Kozielski KL, Wang Y, Jin Y et al. 2015. Polymeric nanoparticles for nonviral gene therapy extend brain tumor survival in vivo. ACS Nano 9:1236–49
     [Google Scholar]
  62. 62. 
    Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM et al. 2014. Chimeric antigen receptor T cells for sustained remissions in leukemia. N. Engl. J. Med. 371:1507–17
     [Google Scholar]
  63. 63. 
    Burnight ER, Staber JM, Korsakov P, Li X, Brett BT et al. 2012. A hyperactive transposase promotes persistent gene transfer of a piggyBac DNA transposon. Mol. Ther. Nucleic Acids 1:e50
     [Google Scholar]
  64. 64. 
    Smith TT, Stephan SB, Moffett HF, McKnight LE, Ji W et al. 2017. In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers. Nat. Nanotechnol. 12:813–20
     [Google Scholar]
  65. 65. 
    Parayath NN, Stephan SB, Koehne AL, Nelson PS, Stephan MT. 2020. In vitro-transcribed antigen receptor mRNA nanocarriers for transient expression in circulating T cells in vivo. Nat. Commun. 11:6080
     [Google Scholar]
  66. 66. 
    Van Hoecke L, Roose K. 2019. How mRNA therapeutics are entering the monoclonal antibody field. J. Transl. Med. 17:54
     [Google Scholar]
  67. 67. 
    Cross R. 2018. Can mRNA disrupt the drug industry?. Chem. Eng. News 96:34–40
     [Google Scholar]
  68. 68. 
    Kariko K, Muramatsu H, Welsh FA, Ludwig J, Kato H et al. 2008. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16:1833–40
     [Google Scholar]
  69. 69. 
    Nallagatla SR, Bevilacqua PC. 2008. Nucleoside modifications modulate activation of the protein kinase PKR in an RNA structure-specific manner. RNA 14:1201–13
     [Google Scholar]
  70. 70. 
    Kariko K, Weissman D. 2007. Naturally occurring nucleoside modifications suppress the immunostimulatory activity of RNA: implication for therapeutic RNA development. Curr. Opin. Drug Disc. 10:523–32
     [Google Scholar]
  71. 71. 
    Muttach F, Muthmann N, Rentmeister A. 2017. Synthetic mRNA capping. Beilstein J. Org. Chem. 13:2819–32
     [Google Scholar]
  72. 72. 
    Li L, Dimitriadis EK, Yang Y, Li J, Yuan Z et al. 2013. Production and characterization of novel recombinant adeno-associated virus replicative-form genomes: a eukaryotic source of DNA for gene transfer. PLOS ONE 8:e69879
     [Google Scholar]
  73. 73. 
    Monjezi R, Miskey C, Gogishvili T, Schleef M, Schmeer M et al. 2017. Enhanced CAR T-cell engineering using non-viral Sleeping Beauty transposition from minicircle vectors. Leukemia 31:186–94
     [Google Scholar]
  74. 74. 
    Schweizer A, Rusert P, Berlinger L, Ruprecht CR, Mann A et al. 2008. CD4-specific designed ankyrin repeat proteins are novel potent HIV entry inhibitors with unique characteristics. PLOS Pathog 4:e1000109
     [Google Scholar]
  75. 75. 
    Tang AA, Tiede C, Hughes DJ, McPherson MJ, Tomlinson DC. 2017. Isolation of isoform-specific binding proteins (Affimers) by phage display using negative selection. Sci. Signal. 10:eaan0868
     [Google Scholar]
  76. 76. 
    Kacherovsky N, Cardle II, Cheng EL, Yu JL, Baldwin ML et al. 2019. Traceless aptamer-mediated isolation of CD8+ T cells for chimeric antigen receptor T-cell therapy. Nat. Biomed. Eng. 3:783–95
     [Google Scholar]
  77. 77. 
    Operti MC, Fecher D, van Dinther EAW, Grimm S, Jaber R et al. 2018. A comparative assessment of continuous production techniques to generate sub-micron size PLGA particles. Int. J. Pharm. 550:140–48
     [Google Scholar]
  78. 78. 
    Leaver T. 2017. Nanoparticles—a revolution in the development of drug delivery vehicles. Drug Development and Delivery https://drug-dev.com/nanoparticles-a-revolution-in-the-development-of-drug-delivery-vehicles/
    [Google Scholar]
  79. 79. 
    Petschacher CEA, Besenhard M, Wagner J, Barthelmes J, Bernkop-Schnuerch A et al. 2013. Thinking continuously: a microreactor for the production and scale-up of biodegradable, self-assembled nanoparticles. Polym. Chem. 4:2342–52
     [Google Scholar]
  80. 80. 
    Patil S, Gao YG, Lin X, Li Y, Dang K et al. 2019. The development of functional non-viral vectors for gene delivery. Int. J. Mol. Sci 20:5491
     [Google Scholar]
  81. 81. 
    Nat. Biotechnol 2019. Moderna jockeys into Harvard. Nat. Biotechnol. 37:1248
     [Google Scholar]
  82. 82. 
    Klichinsky M, Ruella M, Shestova O, Lu XM, Best A et al. 2020. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat. Biotechnol. 38:947–53
     [Google Scholar]
  83. 83. 
    Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P et al. 2020. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. N. Engl. J. Med. 382:545–53
     [Google Scholar]
  84. 84. 
    Kloess S, Kretschmer A, Stahl L, Fricke S, Koehl U. 2019. CAR-expressing natural killer cells for cancer retargeting. Transfus. Med. Hemother. 46:4–13
     [Google Scholar]
  85. 85. 
    Jain R, Frederick JP, Huang EY, Burke KE, Mauger DM et al. 2018. MicroRNAs enable mRNA therapeutics to selectively program cancer cells to self-destruct. Nucleic Acid Ther 28:285–96
     [Google Scholar]
  86. 86. 
    Lokugamage MP, Sago CD, Gan Z, Krupczak BR, Dahlman JE. 2019. Constrained nanoparticles deliver siRNA and sgRNA to T cells in vivo without targeting ligands. Adv. Mater. 31:e1902251
     [Google Scholar]
  87. 87. 
    Araki R, Matsuzaki T, Nakamura A, Nakatani D, Sanada S et al. 2018. Development of a novel one-step production system for injectable liposomes under GMP. Pharm. Dev. Technol. 23:602–7
     [Google Scholar]
  88. 88. 
    Rivnay B, Wakim J, Avery K, Petrochenko P, Myung JH et al. 2019. Critical process parameters in manufacturing of liposomal formulations of amphotericin B. Int. J. Pharm. 565:447–57
     [Google Scholar]
  89. 89. 
    Moffett HF, Coon ME, Radtke S, Stephan SB, McKnight L et al. 2017. Hit-and-run programming of therapeutic cytoreagents using mRNA nanocarriers. Nat. Commun. 8:389
     [Google Scholar]
  90. 90. 
    Stephan MT, Irvine DJ. 2011. Enhancing cell therapies from the outside in: cell surface engineering using synthetic nanomaterials. Nano Today 6:309–25
     [Google Scholar]
  91. 91. 
    Depil S, Duchateau P, Grupp SA, Mufti G, Poirot L. 2020.. ‘ Off-the-shelf’ allogeneic CAR T cells: development and challenges. Nat. Rev. Drug Discov. 19:185–99
     [Google Scholar]
  92. 92. 
    Qasim W. 2019. Allogeneic CAR T cell therapies for leukemia. Am. J. Hematol. 94:S50–54
     [Google Scholar]
  93. 93. 
    Bailey SR, Maus MV. 2019. Gene editing for immune cell therapies. Nat. Biotechnol. 37:1425–34
     [Google Scholar]
  94. 94. 
    Ghosh A, Smith M, James SE, Davila ML, Velardi E et al. 2017. Donor CD19 CAR T cells exert potent graft-versus-lymphoma activity with diminished graft-versus-host activity. Nat. Med. 23:242–49
     [Google Scholar]
  95. 95. 
    Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M et al. 2018. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N. Engl. J. Med. 378:439–48
     [Google Scholar]
  96. 96. 
    Wang X, Popplewell LL, Wagner JR, Naranjo A, Blanchard MS et al. 2016. Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL. Blood 127:2980–90
     [Google Scholar]
  97. 97. 
    Beatty GL, O'Hara MH, Lacey SF, Torigian DA, Nazimuddin F et al. 2018. Activity of mesothelin-specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a Phase 1 trial. Gastroenterology 155:29–32
     [Google Scholar]
  98. 98. 
    Junghans RP, Ma Q, Rathore R, Gomes EM, Bais AJ et al. 2016. Phase I trial of anti-PSMA designer CAR-T cells in prostate cancer: possible role for interacting interleukin 2-T cell pharmacodynamics as a determinant of clinical response. Prostate 76:1257–70
     [Google Scholar]
  99. 99. 
    Ghassemi S, Nunez-Cruz S, O'Connor RS, Fraietta JA, Patel PR et al. 2018. Reducing ex vivo culture improves the antileukemic activity of chimeric antigen receptor (CAR) T cells. Cancer Immunol. Res. 6:1100–9
     [Google Scholar]
  100. 100. 
    Themeli M, Kloss CC, Ciriello G, Fedorov VD, Perna F 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]
  101. 101. 
    Li Y, Hermanson DL, Moriarity BS, Kaufman DS. 2018. Human iPSC-derived natural killer cells engineered with chimeric antigen receptors enhance anti-tumor activity. Cell Stem Cell 23:181–92.e5
     [Google Scholar]
  102. 102. 
    Shukla S, Langley MA, Singh J, Edgar JM, Mohtashami M et al. 2017. Progenitor T-cell differentiation from hematopoietic stem cells using Delta-like-4 and VCAM-1. Nat. Methods 14:531–38
     [Google Scholar]
  103. 103. 
    Seet CS, He C, Bethune MT, Li S, Chick B et al. 2017. Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids. Nat. Methods 14:521–30
     [Google Scholar]
  104. 104. 
    Yagyu S, Hoyos V, Del Bufalo F, Brenner MK. 2015. An inducible caspase-9 suicide gene to improve the safety of therapy using human induced pluripotent stem cells. Mol. Ther. 23:1475–85
     [Google Scholar]
  105. 105. 
    Giordano SH, Niu J, Chavez-MacGregor M, Zhao H, Zorzi D et al. 2016. Estimating regimen-specific costs of chemotherapy for breast cancer: observational cohort study. Cancer 122:3447–55
     [Google Scholar]
  106. 106. 
    Abou-El-Enein M, Bauer G, Medcalf N, Volk HD, Reinke P. 2016. Putting a price tag on novel autologous cellular therapies. Cytotherapy 18:1056–61
     [Google Scholar]
  107. 107. 
    Dobrovolskaia MA, McNeil SE 2013. Preface. Handbook of Immunological Properties of Engineered Nanomaterials, ed. MA Dobrovolskaia, SE McNeil xix–xxi Singapore: World Sci.
     [Google Scholar]
  108. 108. 
    de Vlieger JSB, Crommelin DJA, Tyner K, Drummond DC, Jiang WL et al. 2019. Report of the AAPS Guidance Forum on the FDA draft guidance for industry: “Drug Products, Including Biological Products, that Contain Nanomaterials. .” AAPS J 21:56
     [Google Scholar]
  109. 109. 
    Yeager AJ. 2017. CAR-T in the courts. Genet. Eng. Biotechnol. News 37:1931–33
     [Google Scholar]
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In Situ Programming of CAR T Cells
Annual Review of Biomedical Engineering 23, 385 (2021); https://doi.org/10.1146/annurev-bioeng-070620-033348
/content/journals/10.1146/annurev-bioeng-070620-033348
/content/journals/10.1146/annurev-bioeng-070620-033348
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