Table 2 CRISPR/Cas9-mediated gene therapy targets for enhancing TCR and CAR T-cell function
From: CRISPR/Cas9 revitalizes adoptive T-cell therapy for cancer immunotherapy
Cell type | Manipulation | Gene | Protein | Cancer Type | Summary | Advantage | Disadvantage |
|---|---|---|---|---|---|---|---|
CAR T-cell | Universal CAR T-cells | TRAC/TRBC | TCRαβ | Acute Lymphoblastic Leukemia | Knocking out endogenous TCR chains reduces the likelihood of GVHD | Creates convenient, cheap, and rapid allogeneic CAR T-cells | HLA-I elimination could increase reactions from NK cells and lower the efficacy of therapy |
B2M | Acute Lymphoblastic Leukemia | ||||||
Immune checkpoint blockade | PDCD1 | PD-1 | Hepatocellular Carcinoma | Singular or concurrent knockout of immune checkpoint inhibitors diminishes CAR T-cell exhaustion and increases cytotoxicity and proliferation | Creates more active and robust CAR T-cells | A potential risk of autoimmunity and off-target effects | |
CTLA-4 | CTLA-4 | Acute Lymphoblastic Leukemia | |||||
LAG-3 | LAG-3 | Chronic Myelogenous Leukemia | |||||
Fas | CD94 | Acute Lymphoblastic Leukemia | |||||
TGFBR2 | TGF-β | Squamous Cell Carcinoma | |||||
Cytokine production | DGKA/DGKZ | DGK | Glioblastoma | Cytokines are pivotal in promoting CAR T-cell activation and function | Creates more persistent and cytotoxic CAR T-cell | A potential risk of CAR T-cell exhaustion/ limited knock-in efficacy | |
TCR T-cell | Universal TCR T-cells | TRAC/TRBC | TCRαβ | Acute Lymphoblastic Leukemia | Knocking out endogenous TCR chains reduces the likelihood of GVHD | Creates convenient, cheap, and rapid allogeneic TCR T-cells | HLA-I elimination could increase reactions from NK cells and lower the efficacy of therapy |
B2M | Acute Lymphoblastic Leukemia | ||||||
Immune checkpoint blockade | PD-1 | PD-1 | Melanoma/ Renal Cell Carcinoma | Singular or concurrent knockout of immune checkpoint inhibitors diminishes TCR T-cell exhaustion and increases cytotoxicity and proliferation | Creates more active and robust TCR T-cells | A potential risk of autoimmunity and off-target effects | |
CTLA-4 | CTLA-4 | Bladder Cancer | |||||
LAG-3 | LAG-3 | Chronic Myelogenous Leukemia | |||||
TGFBR2 | TGF-β | Ovarian Cancer | |||||
Cytokine production | Dhx37 | DHX37 | Breast Cancer | Cytokines are pivotal in promoting CAR T-cell activation and function | Creates more active and robust TCR T-cells | A potential risk of TCR T-cell exhaustion/ limited knock-in efficacy | |
Nr2f6 | NR2F6 | Colon Carcinoma | |||||
Gata3 | GATA3 | Colon Carcinoma | |||||
IFNG | IFN-γ | Melanoma |