Table 1.
Novel genetic modifications in cytokine, chemokine and their receptors to enhance the efficacy of CAR T cell therapy.
| Strategies | Cytokines & Chemokines | Genetic modification | Reference |
|---|---|---|---|
| Improving persistence | IL-15 & IL-21 | Overexpression | (23) |
| IL-7 & CCL9 | Overexpression | (24) | |
| IL-15 | Overexpression | (25, 26) | |
| TGFβ | CRISPR-mediated knockout | (27) | |
| IL-7 | ICR | (28) | |
| Converting immuno-suppressive to immuno-promoting signals | IL-4R/IL-7R | ICR | (29) |
| IL-4R/IL-21R | ICR | (22) | |
| TGFβ/IL-7R | ICR | (30) | |
| GM-CSF/IL-18R | ICR | (31) | |
| Overcoming Exhaustion | TGFβRII | Truncated | (15) |
| CRISPR-mediated knockout | (27) | ||
| aPD1/TGFβ trap | Overexpression | (32) | |
| IL-18 | Inducible expression | [20] | |
| IL-7 | Overexpression | (33) | |
| IL-15 | Membrane tethered | (34) | |
| AICD prevention | IL-7 | ICR | (28) |
| IL-15 | Membrane tethered | (34) | |
| Improving infiltration | CCR6 | Overexpression | (35) |
| CCR2b | Overexpression | (18, 36) | |
| CCR4 | Overexpression | (37) | |
| CXCR2 | Overexpression | (38) | |
| CRS and neurotoxicity inhibition | IL-6 | shRNA-mediated Knockdown | (39) |
| mbaIL-6 | Truncated | (40) | |
| GM-CSF | CRISPR-mediated knockout | (41) | |
| GM-CSF & aIL-6/IL-1RA | CRISPR-mediated knockout & secreting neutralizing antibody & antagonist | (14) | |
| Endogenous immune system activation | IL-7 & CCL19 | Overexpression | (24) |
| IL-18 | Overexpression | (42) | |
| IL-12 | Overexpression | (43, 44) | |
| IL-36γ | Overexpression | (45) |
ICR: inverted cytokine receptor; CRS: cytokine release syndrome; mbaIL6: membrane-bound IL-6 receptor; aIL-6R: anti-IL-6 receptor antibody; IL-1RA: IL-1 receptor antagonist.