From: Gene modification strategies for next-generation CAR T cells against solid cancers
Negative regulators | Name | Malignancy | Genome editing tool | Function | Reference(s) |
---|---|---|---|---|---|
Immune checkpoint molecules | PD-1 | ALL, CML, TNBC, HCC, Glioma | CRISPR-Cas9, TALEN, AAV–Cpf1 | Improved cytokine production, infiltration and persistence of CAR T cells; enhanced tumor clearance | |
CTLA-4 | NMIBC, CML | CRISPR-Cas9 | Improved CAR T cell function | ||
LAG3 | Burkitt lymphoma, CML | CRISPR-Cas9 | Improved CAR T cell function | [121] | |
Transcription factors | NR4A | Melanoma, Thymoma, COAD | — | Promoted tumor regression | [122] |
TOX | Melanoma, COAD | shRNAs | Augmented antitumor responses | [123] | |
Metabolic molecules | DGKs | GBM | CRISPR-Cas9 | Increased TCR signaling in CAR T cells; enhanced CAR T cell effector function | [124] |
Apoptotic genes | Fas | ALL, CML | CRISPR-Cas9 | Increased tolerance of CAR T cells to apoptosis | [119] |