Table 1.
The main preclinical studies targeting coinhibitory or co-stimulatory receptors.
| Target | Effects | Tumor type | Species | Combined therapy | Ref |
|---|---|---|---|---|---|
| PD1 |
Anti PD-1 therapy
1. In vivo; 2. Inhibited tumor growth; 3. Expanded Tpex and promoted Tpex differentiate into terminally exhausted cells with better effector function; |
Melanoma (B16-OVA) | M | / | (5) |
|
Anti PD-1 therapy
1. In vivo; 2. Expanded Tpex and promoted Tpex differentiate into terminally exhausted cells; |
Melanoma (B16) |
M | / | (15) | |
| CTLA-4 |
Anti CTLA-4 antibody
1. In vivo; 2. Prolonged survival; 3. Expanded CD8+ TILs and increased IFN-γ production; |
Ovarian cancer (OVCAR5) |
M | PD1/PDL1 blockade | (46) |
| 4-1BB |
4-1BB agonistic antibody
1. In vivo; 2. limited tumor progression; 3 .Improved the metabolic sufficiency of CD8+ TILs; |
Melanoma (B16-F10) |
M | PD1/PDL1 blockade | (46) |
|
4-1BB agonistic antibody
1. In vivo; 2. Prolonged survival; 3. Increased numbers of CD8+ TILs with greater IFN-γ production and the decreased expression of PD-1, TIM3, and LAG3; |
Glioblastoma (CT2A) | M | PD1/PDL1 blockade | (50) | |
|
4-1BB agonistic antibody
1. Ex vivo (co-cultured drug with CD8+ TILs from patients) 2. Promoted proliferative capacity and cytokine production; |
Liver cancer | H | PD1/PDL1 blockade | (18) | |
|
4-1BB agonistic antibody
1. Ex vivo (co-cultured drug with CD8+ TILs from patients); 2. Enhanced proliferation and production of IFN-γ and TNF-α in CD8+ TILs; |
Ovarian cancer | H | PD1/PDL1 blockade | (51) | |
|
4-1BB-CD3zeta CAR-T cells
1. ACT (transfer of 4-1BB-CD3zeta CAR-T cells into tumor models); 2. Exerted persistent anti-tumor activity; 3. 4-1BB-CD3zeta CAR-T cells expressed genes involved in T-cell memory program; |
Lymphoma (Raji) | M | / | (52) |
The table summarized the main preclinical studies of targeting coinhibitory or co-stimulatory receptors. Tumor, tumor cell lines in mouse model or method. H, human, M, mouse; Ref, references; ACT, adoptive cell transfer therapy.