Table 2.
The main preclinical studies of transcription factor-based therapy.
| Target | Effects | Tumor type | Species | Combined therapy | Ref |
|---|---|---|---|---|---|
| NFAT: AP-1 complex |
c-Jun OE (CAR-T cells overexpressing c-Jun)
1. ACT (Transfer of c-Jun OE into tumor models) 2. Limited tumor growth; 3. c-Jun OE showed enhanced expansion potential, cytotoxicity and diminished terminal exhaustion differentiation; |
Leukemia (Nalm6-GD2); Osteosarcoma (143B) |
M | / | (12) |
|
Knockdown Nrp1 in CD8+ T cells
1. Evaluated the anti-tumor effects of Knockdown Nrp1 in CD8+ T cells; 2. Increased the frequency of Tpex and memory T cells in TME; 3. Exhibited greater effector function upon re-stimulation and promoted long-term immunity; |
Melanoma (B16) | M | PD1/PDL1 blockade | (57) | |
| TOX |
Tox DKO (TOX1, TOX2) CAR-T cells
1. ACT (transfer of Tox DKO CAR-T cells into tumor models); 2. Limited tumor growth; 3. Promoted cytokine production (TNF, IFN-γ); 4. Downregulated the expression of inhibitory receptors (PD-1, TIM3 and LAG3); |
Melanoma (B16) |
M | / | (30) |
|
TOX-knockout tumor-specific T cells
1. ACT (transfer of TOX-knockout tumor-specific T cells into tumor models); 2. TOX-knockout tumor-specific T cells showed: 3. Non-exhausted phenotype; 4. Loss of effector function; 5. Increased apoptosis; |
Melanoma (B16) |
M | / | (22) | |
|
Anti-VEGFR2 antibody
1. In vivo; 2. Suppressed tumor growth and prolonged survival; 3. Decreased the level of TOX; 4. Reduced the expression of inhibitory receptors (TIM3, LAG3 and TIGIT); 5. Increased IFN-γ and TNF production; |
Colon cancer (MC38-OVA) | M | PD1/PDL1 blockade | (59) | |
| NR4A |
NR4A-deficient CAR-T cells
1. ACT (transfer of NR4A-deficient CAR-T cells into tumor models) 2. Suppressed tumor growth; 3. Promoted cytokine production (TNF, IFN-γ); 4. Downregulated the expression of inhibitory receptors; |
Melanoma (B16) |
M | / | (30) |
| TCF1 |
Ectopic TCF-1 expression
1. Evaluated the anti-tumor effects of ectopic TCF-1 expression; 2. Suppressed tumor growth; 3. Significant expansion of Tpex and terminally exhausted subsets; 4. Enhanced cytokine production and decreased expression of co-inhibitory receptors in terminally exhausted subsets; |
Melanoma (B16) |
M | / | (44) |
|
Regnase-1-deficient CAR-T cells
1. ACT (transfer of Regnase-1-deficient CAR-T cells into tumor models); 2. Enhanced tumor clearance; 3. CAR-T cells showed the features of Tpex and long-term persistence in TME; |
ALL (h CD19+ B-ALL cells) |
M | / | (60) | |
|
Ectopic NELF expression
1. Evaluated the anti-tumor effects of ectopic NELF expression; 2. Boosted anti-tumor immunity; 3. Improved the proliferative and cytotoxic function of CD8+ TILs; |
Breast cancer (E0771, AT3) | M | / | (61) |
The table summarized the main preclinical studies of transcription factor-based therapy. Tumor: tumor cell lines in mouse model or method. M, mouse; Ref, references; ACT, adoptive cell transfer therapy.