production of universal CAR-T cell via disturbing endogenous genes |
TCR/B2M |
Prevention of GvH and rejection |
Liu X, et al. 2017.2727 Liu X, Zhang Y, Cheng C, Cheng AW, Zhang X, Li N, e al. CRISPR-Cas9-mediated multiplex gene editing in CAR-T cells. Cell Res. 2017;27(1):154-7. https://doi.org/10.1038/nature214 https://doi.org/10.1038/nature214...
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TRAC (TCR knockout and CAR knock-in) /B2M |
uniform CAR expression, Prevention of GvH and rejection |
Eyquem J, et al. 2017.2828 Eyquem J, Mansilla-Soto J, Giavridis T, van der Stegen SJ, Hamieh M, Cunanan KM, et al. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature. 2017;543(7643):113-7. https://doi.org/10.1038/nature21405 https://doi.org/10.1038/nature21405...
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TRAC/CD52 |
Prevention of GvH, T cell resistance to lymphodepletion. |
Li C, et al. 2020.2929 Li C, Mei H, Hu Y. Applications and explorations of CRISPR/Cas9 in CAR T-cell therapy. Brief Funct Genomics. 2020;19(3):175-82. https://doi.org/10.1093/bfgp/elz042. https://doi.org/10.1093/bfgp/elz042...
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Pax5 or Ebf1 |
Recapitulation of lineage switch following pressure on the B-cell lineage by CD19 CAR (only in ALL) with the capacity to utilize this mechanism for resistance to CD19-targeted immunotherapy. |
Jacoby E, 2016. 3030 Jacoby E, Nguyen SM, Fountaine TJ, Welp K, Gryder B, Qin H, et al. CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity. Nat Communic. 2016 27;7(1):1-0. https://doi.org/10.1038/ncomms12320. https://doi.org/10.1038/ncomms12320...
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CAR T cell functional augmentation by broadening the range of untargetable CAR antigen |
CD5 |
Elimination of fratricide |
Fleischer LC, et al. 2017.3131 Fleischer LC, Raikar SS, Moot R, Knight KA, Doering CB, Spencer HT. Engineering CD5-targeted chimeric antigen receptors and edited T cells for the treatment of T-Cell Leukemia. Blood 130: 1914. https://doi.org/10.1182/blood.V130.Suppl_1.1914.1914 https://doi.org/10.14348/molcells.2018.0242 https://doi.org/10.1182/blood.V130.Suppl...
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CD7 |
Elimination of fratricide |
Gomes-Silva D, et al. 2017.3232 Gomes-Silva D, Srinivasan M, Sharma S, Lee CM, Wagner DL, Davis TH, et al. CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies. Blood. 2017; 20;130(3):285-96. https://doi.org/10.1182/blood-2017-01-761320 https://doi.org/10.1182/blood-2017-01-76...
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GM-CSF |
Reduction of CRS |
Sterner RM, et al. 2019.3333 Sterner RM, Cox MJ, Sakemura R, Kenderian SS. Using CRISPR/Cas9 to knock out GM-CSF in CAR-T cells. JoVE. 2019;(149):e59629. https://doi.org/10.3791/59629. https://doi.org/10.3791/59629...
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Diacylglycerol Kinase (DGK) |
increasing TCR signaling |
Jung IY, et al. 2018.3434 Jung IY, Kim YY, Yu HS, Lee M, Kim S, Lee J. CRISPR/Cas9-mediated knockout of DGK improves antitumor activities of human T cells. Cancer Res. 2018;78(16):4692-703. https://doi.org/10.1158/0008-5472.CAN-18-0030 https://doi.org/10.1158/0008-5472.CAN-18...
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knock-out checkpoint inhibitors |
LAG-3 |
abrogation of tumor growth |
Zhang Y, et al. 2017.3535 Zhang Y, Zhang X, Cheng C, Mu W, Liu X, Li N, et al. CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells. Front Med. 2017;11(4):554-62. https://doi.org/10.1007/s11684-017-0543-6. https://doi.org/10.1007/s11684-017-0543-...
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PD-1 |
abrogation of tumor growth |
Ren J, et al. 2017. 3636 Ren J, Zhang X, Liu X, Fang C, Jiang S, June CH, et al.. A versatile system for rapid multiplex genome-edited CAR T cell generation. Oncotarget. 2017;8(10):17002. https://doi.org/10.18632/oncotarget.15218. https://doi.org/10.18632/oncotarget.1521...
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CTLA-4 |
abrogation of tumor growth |
Ren J, et al. 2017.3636 Ren J, Zhang X, Liu X, Fang C, Jiang S, June CH, et al.. A versatile system for rapid multiplex genome-edited CAR T cell generation. Oncotarget. 2017;8(10):17002. https://doi.org/10.18632/oncotarget.15218. https://doi.org/10.18632/oncotarget.1521...
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Fas |
elevation of activation-induced cell death (AICD) resistance and prolonged survival. |
Ren J, et al. 2017.3636 Ren J, Zhang X, Liu X, Fang C, Jiang S, June CH, et al.. A versatile system for rapid multiplex genome-edited CAR T cell generation. Oncotarget. 2017;8(10):17002. https://doi.org/10.18632/oncotarget.15218. https://doi.org/10.18632/oncotarget.1521...
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TGF-βRII |
Reducing induced Treg conversion and preventing exhaustion of CAR T cells. |
Tang N, et al. 2020.3737 Tang N, Cheng C, Zhang X, Qiao M, Li N, Mu W, et al.. TGF-β inhibition via CRISPR promotes the long-term efficacy of CAR T cells against solid tumors. JCI insight. 2020;5(4). https://doi.org/10.1172/jci.insight.133977. https://doi.org/10.1172/jci.insight.1339...
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