Table 3.
The main preclinical studies of epigenetic therapy.
| Target/ Process |
Effects | Tumor type | Species | Combined therapy | Ref |
|---|---|---|---|---|---|
| DNA methylation |
Decitabine (DAC)
1. In vivo; 2. Mainly evaluated the efficacy when combined with anti-PD1 therapy; 3. Combined therapy inhibited tumor growth; 4. CD8+ TILs resisted exhaustion and maintained greater expansion potential; |
Prostate Cancer (TRAMP-C2) |
M | PD1/PDL1 blockade | (42) |
|
Decitabine (DAC)
1. In vivo; 2. Mainly evaluated the efficacy when combined with anti-PD1 therapy; 3. Combined therapy promoted Tpex expansion; 4. Increased secretion of IFN-γ and TNF-α; 5. Potentiated CD8+ T cell response; |
Colon cancer (MC38); T cell Lymphoma (EG7) |
M | PD1/PDL1 blockade | (19) | |
| DNMT3A |
DNMT3A knockout CAR-T cells
1. ACT (transfer of DNMT3A knockout CAR-T cells into tumor models); 2. Slowed down tumor growth and prolonged survival; 3. Differentiated into stem-like CAR-T cells in TME; 4. Maintained long-term anti-tumor responses; |
Breast cancer (LM7); Glioma (U373) |
M | / | (13) |
| Kdm6b |
Overexpressing Kdm6b on T cells
1. ACT (transfer of Kdm6b overexpressing on T cells into tumor models); 2. Limited tumor growth; 3. Achieved better cytotoxicity; 4. No effects on the differentiation program to exhaustion; |
Melanoma (B16) |
M | / | (32) |
| LSD1 |
LSD1 blockade
1. In vivo; 2. Limited tumor growth; 3. Mainly expanded Tpex; |
Colon cancer (MC38) | M | PD1/PDL1 blockade | (66) |
|
LSD1 inhibitor
1. In vivo; 2. Inhibited tumor progression; 3. Increased CD8+ T cell infiltration and proliferative capacity; |
Breast cancer (EMT6; 4T1) | M | PD1/PDL1 blockade | (67) | |
|
nLSD1 blockade
1. In vivo 2. Increased CD8+ T cell infiltration, particularly the IFN-γ+ CD8+ T cells; 3. Decreased the expression of TIGIT, LAG3 and TIM3 on CD8+ TILs; |
Breast cancer (4T1 TNBC; MDA-MB-231 TNBC) |
M | PD1/PDL1 blockade | (68) | |
| Arid1a |
Arid1a-deficient CAR-T cells
1. ACT (transfer of Arid1a-deficient CAR-T cells into tumor models); 2. Prevented acquirement of exhaustion-related chromatin accessibility; 3. Drove the differentiation into memory T cells; |
Colon cancer (MC38) | M | / | (43) |
|
Arid1a inhibitor
1.ACT (tansfer of Naive CD8+ T cells pre-treat with Arid1a inhibitor); 2. Suppressed tumor growth; 3. CAR-T cells showed greater persistence and better anti-tumor activity; |
Melanoma (B16); Colon cancer (MC38) |
M | / | (69) | |
| PAC1 |
Knockdown pac1
1. Evaluated the anti-tumor effects of knockdown of pac1; 2. Limited tumor growth; 3. Increased CD8+ TILs; 4. Increased production of IFN-γ and TNF in CD8+ TILs; 5. Potentiated CD8+ T cell response; |
Colon cancer (AOM-DSS model); Melanoma (B16-F10) |
M | / | (40) |
The table summarized the main preclinical studies of epigenetic therapy. Tumor: tumor cell lines in mouse model or method. M, mouse; Ref, references; ACT, adoptive cell transfer therapy.