Display options
Share it on

Cancer Discov. 2021 Mar;11(3):560-574. doi: 10.1158/2159-8290.CD-20-1083. Epub 2021 Feb 09.

Applications of CRISPR Genome Editing to Advance the Next Generation of Adoptive Cell Therapies for Cancer.

Cancer discovery

Samantha M Fix, Amir A Jazaeri, Patrick Hwu

Affiliations

  1. Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  2. Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  3. Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. [email protected].

PMID: 33563662 PMCID: PMC8193798 DOI: 10.1158/2159-8290.CD-20-1083

Abstract

Adoptive cell therapy (ACT) for cancer shows tremendous potential; however, several challenges preclude its widespread use. These include poor T-cell function in hostile tumor microenvironments, a lack of tumor-specific target antigens, and the high cost and poor scalability of cell therapy manufacturing. Creative genome-editing strategies are beginning to emerge to address each of these limitations, which has initiated the next generation of cell therapy products now entering clinical trials. CRISPR is at the forefront of this revolution, offering a simple and versatile platform for genetic engineering. This review provides a comprehensive overview of CRISPR applications that have advanced ACT. SIGNIFICANCE: The clinical impact of ACT for cancer can be expanded by implementing specific genetic modifications that enhance the potency, safety, and scalability of cellular products. Here we provide a detailed description of such genetic modifications, highlighting avenues to enhance the therapeutic efficacy and accessibility of ACT for cancer. Furthermore, we review high-throughput CRISPR genetic screens that have unveiled novel targets for cell therapy enhancement.

©2021 American Association for Cancer Research.

References

  1. Methods Mol Biol. 2020;2111:59-70 - PubMed
  2. Nat Med. 2018 Aug;24(8):1216-1224 - PubMed
  3. Cell. 2018 Dec 13;175(7):1958-1971.e15 - PubMed
  4. Mol Ther. 2016 Mar;24(3):570-81 - PubMed
  5. Nature. 2016 Apr 20;533(7603):420-4 - PubMed
  6. Sci Rep. 2018 Apr 3;8(1):5549 - PubMed
  7. Cell Stem Cell. 2020 Aug 6;27(2):224-237.e6 - PubMed
  8. N Engl J Med. 2018 Feb 1;378(5):439-448 - PubMed
  9. iScience. 2020 Jan 24;23(1):100789 - PubMed
  10. Curr Opin Immunol. 2018 Apr;51:146-153 - PubMed
  11. Nat Commun. 2019 Nov 19;10(1):5222 - PubMed
  12. Nat Methods. 2017 Jul;14(7):710-712 - PubMed
  13. Cell. 2018 May 31;173(6):1439-1453.e19 - PubMed
  14. Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10972-7 - PubMed
  15. J Clin Oncol. 1992 Jun;10(6):960-8 - PubMed
  16. Blood. 2011 Sep 29;118(13):3528-37 - PubMed
  17. Nature. 2016 Jan 28;529(7587):490-5 - PubMed
  18. N Engl J Med. 1988 Dec 22;319(25):1676-80 - PubMed
  19. J Exp Med. 2018 Mar 5;215(3):985-997 - PubMed
  20. N Engl J Med. 1985 Dec 5;313(23):1485-92 - PubMed
  21. Mol Ther. 2018 Feb 7;26(2):456-467 - PubMed
  22. Sci Transl Med. 2011 Aug 10;3(95):95ra73 - PubMed
  23. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10024-8 - PubMed
  24. Blood. 2018 Jan 18;131(3):311-322 - PubMed
  25. Curr Protoc Immunol. 2019 Feb;124(1):e69 - PubMed
  26. Sci Transl Med. 2013 Mar 20;5(177):177ra38 - PubMed
  27. J Vis Exp. 2018 Jun 14;(136): - PubMed
  28. BMJ. 2020 Apr 6;369:m736 - PubMed
  29. Nature. 2019 Dec;576(7787):471-476 - PubMed
  30. Leukemia. 2019 Mar;33(3):762-808 - PubMed
  31. Cell. 2019 Aug 22;178(5):1189-1204.e23 - PubMed
  32. Blood. 2017 Jul 20;130(3):285-296 - PubMed
  33. Mol Ther. 2020 Jan 8;28(1):52-63 - PubMed
  34. Am Soc Clin Oncol Educ Book. 2019 Jan;39:433-444 - PubMed
  35. Hum Gene Ther. 2019 Apr;30(4):446-458 - PubMed
  36. Nature. 2017 Mar 2;543(7643):113-117 - PubMed
  37. Clin Cancer Res. 2012 Dec 15;18(24):6758-70 - PubMed
  38. Nat Biotechnol. 2018 Mar;36(3):265-271 - PubMed
  39. Oncoimmunology. 2016 Nov 22;6(1):e1249558 - PubMed
  40. Proc Natl Acad Sci U S A. 2019 Jun 11;116(24):11978-11987 - PubMed
  41. Front Oncol. 2019 Nov 21;9:1237 - PubMed
  42. Cell Rep. 2017 Aug 1;20(5):1017-1028 - PubMed
  43. N Engl J Med. 2020 Feb 6;382(6):545-553 - PubMed
  44. Nature. 2018 Aug;560(7718):382-386 - PubMed
  45. Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):10437-42 - PubMed
  46. Proc Natl Acad Sci U S A. 2018 Apr 24;115(17):E4051-E4060 - PubMed
  47. Nat Med. 2018 Jan;24(1):20-28 - PubMed
  48. Nature. 2018 Jun;558(7709):307-312 - PubMed
  49. Clin Cancer Res. 2015 Nov 15;21(22):5008-12 - PubMed
  50. Nature. 2019 Dec;576(7785):149-157 - PubMed
  51. Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16168-73 - PubMed
  52. Oncoimmunology. 2017 Dec 26;7(3):e1407898 - PubMed
  53. Nat Rev Clin Oncol. 2019 Jun;16(6):372-385 - PubMed
  54. Cancer Res. 2018 Aug 15;78(16):4692-4703 - PubMed
  55. Nature. 2017 Nov 23;551(7681):464-471 - PubMed
  56. JCI Insight. 2020 Feb 27;5(4): - PubMed
  57. N Engl J Med. 2019 Sep 26;381(13):1240-1247 - PubMed
  58. J Clin Invest. 2020 Feb 3;130(2):673-685 - PubMed
  59. J Biotechnol. 2015 Aug 20;208:44-53 - PubMed
  60. Mol Ther Nucleic Acids. 2019 Jun 7;16:326-334 - PubMed
  61. J Immunother Cancer. 2019 Dec 4;7(1):341 - PubMed
  62. Mol Ther. 2020 Jan 8;28(1):64-74 - PubMed
  63. Leukemia. 2018 Nov;32(11):2307-2315 - PubMed
  64. N Engl J Med. 1987 Apr 9;316(15):889-97 - PubMed
  65. Trends Biotechnol. 2019 Jan;37(1):38-55 - PubMed
  66. Science. 2016 Sep 16;353(6305): - PubMed
  67. J Clin Oncol. 2016 Jul 10;34(20):2389-97 - PubMed
  68. J Immunol Methods. 2018 Jun;457:33-40 - PubMed
  69. Sci Transl Med. 2015 Sep 2;7(303):303ra139 - PubMed
  70. Cancer Res. 1989 Jan 1;49(1):235-40 - PubMed
  71. Sci Rep. 2017 Apr 7;7(1):737 - PubMed
  72. Cell. 2020 Apr 30;181(3):728-744.e21 - PubMed
  73. Nat Biotechnol. 2019 Nov;37(11):1302-1313 - PubMed
  74. Nature. 2018 Jul;559(7714):405-409 - PubMed
  75. J Immunol. 1999 Feb 15;162(4):2227-34 - PubMed
  76. Clin Cancer Res. 2013 Sep 1;19(17):4792-800 - PubMed
  77. Nat Med. 2020 May;26(5):732-740 - PubMed
  78. Blood. 2021 Feb 4;137(5):624-636 - PubMed
  79. Nature. 2017 Oct 19;550(7676):407-410 - PubMed
  80. Int Immunol. 2018 Apr 3;30(4):141-154 - PubMed
  81. Blood. 2013 Aug 22;122(8):1341-9 - PubMed
  82. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):720-4 - PubMed
  83. Cancer Immunol Immunother. 2019 Mar;68(3):365-377 - PubMed
  84. Science. 2014 Nov 28;346(6213):1258096 - PubMed
  85. Leukemia. 2018 Sep;32(9):1970-1983 - PubMed
  86. Clin Cancer Res. 2017 May 1;23(9):2255-2266 - PubMed
  87. Bioconjug Chem. 2018 Feb 21;29(2):445-450 - PubMed
  88. Mol Cell. 2017 Sep 21;67(6):1068-1079.e4 - PubMed
  89. Science. 2006 Oct 6;314(5796):126-9 - PubMed
  90. Nat Methods. 2018 Nov;15(11):941-946 - PubMed
  91. PLoS One. 2014 Dec 26;9(12):e115987 - PubMed
  92. Blood. 2010 Nov 18;116(20):4099-102 - PubMed
  93. Clin Cancer Res. 2012 Sep 1;18(17):4514-21 - PubMed
  94. Sci Rep. 2016 Jan 28;6:20070 - PubMed
  95. J Immunother Cancer. 2019 Nov 14;7(1):304 - PubMed
  96. Int J Pharm. 2015 Oct 15;494(1):180-94 - PubMed
  97. Science. 2020 Feb 28;367(6481): - PubMed
  98. J Exp Med. 1993 Jul 1;178(1):361-6 - PubMed
  99. Front Pharmacol. 2018 Oct 01;9:1118 - PubMed
  100. Blood Rev. 2019 Nov;38:100596 - PubMed
  101. Cell Res. 2017 Jan;27(1):154-157 - PubMed
  102. Clin Cancer Res. 2016 Aug 1;22(15):3734-45 - PubMed

Publication Types

Grant support