Table 4 Preclinical studies of ICIs combine with co-stimulatory receptors
Author, year | Receptor and ligands | ICI | Combination | Treatment | Model | Anti-tumor efficacy |
|---|---|---|---|---|---|---|
Chan et al. 2022 [46] | GITR | Anti-PD-1 antibody | Multimeric GITR ligand | Anti-PD-1–GITR- ligand bispecific antibody | CT26, EMT6 and JC tumor mouse models | 1. Induced CD8+ T cell infiltration and Tregs depletion 2. Inhibited tumor growth and prolongs OS |
Zappasodi et al. 2019 [359] | GITR | Anti-PD-1 antibody | Anti-GITR antibody | Anti-PD-1 antibody + TRX518 | B16F10 tumor mouse model | 1. Induced CD8+ T cell infiltration and Tregs death 2. Induced tumor regression |
Ma et al. 2019 [39] | OX40 | Anti-PD-1 antibody | Anti-OX40 agonist antibody | Anti-PD-1 antibody + anti-OX40 agonist antibody | PDAC mouse model | 1. Enhanced the infiltration of CD4+ T cells and CD8+ T cells, 2. Prolonged the survival of mice and promoted tumor regression compared with monotherapy |
Lao et al. 2020 [360] | OX40 | Anti-PD-1 antibody | Anti-OX40 agonist antibody | Anti-PD-1 antibody + anti-OX40 agonist antibody | NSCLC mouse model | 1. Stimulated the activation of CD4+ T cells and CD8+ T cells 2. Reduced tumor tissue |
Guo et al. 2021 [361] | OX40 | Anti-PD-1 antibody | Anti-OX40 agonist antibody | Anti-PD-1 antibody + anti-OX40 agonist antibody | ID8 tumor mouse model | 1. Increased CD4+ T cells and CD8+ T cells, and decreased Tregs and MDSCs 2. Inhibited tumor growth |
Qu et al. 2022 [352] | 4-1BB | Anti-PD-L1 antibody | Anti-4-1BB antibody | Anti-PD-L1 antibody + anti-4-1BB antibody | 3LL and 4T1.2 tumor mouse models | 1. Induced CD8+T cells infiltration 2. Improved survival and induced tumor regression compared with monotherapy |
Jeong et al. 2019 [362] | 4-1BB | Anti-PD-L1 antibody | Anti-4-1BB antibody | ABL503 (4-1BB × PD-L1 bispecific antibody) | MC38hPD−L1 tumor mouse model | 1. Induced CD8+ T cells activation 2. Resulted in almost complete tumor regression and prolonged survival in mice |
Wang et al. 2022 [363] | 4-1BB | Anti-PD-L1 antibody | 4-1BB agonist | Anti-PD-L1 antibody + 4-1BB agonist | A20 and WEHI-231 tumor mouse model | 1. Induced CD8+ T cells infiltration 2. Results in a relative tumor weight of 5.0 ± 4.6%, as compared with 66.8 ± 7.5% with anti-PD-L1 antibody monotherapy, and prolonged survival |
Soldevilla et al. 2019 [355] | ICOS | Anti-CTLA-4 antibody | ICOS bi-specific agonistic aptamer | Anti-CTLA-4 antibody + ICOS bi-specific agonistic aptamer | Highly aggressive melanoma mouse models | 1. Induced CD8+ T cells infiltration 2. Inhibited tumor growth |
Fan et al. 2014 [364] | ICOS | Anti-CTLA-4 antibody | Vaccines engineered to express ICOS ligand | Anti-CTLA-4 antibody + vaccines engineered to express ICOS ligand | B16/F10 and TRAMP C2 tumor mouse model | 1. Induced CD8+ T cells infiltration 2. Improved tumor rejection and OS |
Diggs et al. 2019 [358] | CD40 | Anti-PD-1 antibody | CD40 agonist | Anti-PD-1 antibody + CD40 agonist | Intrahepatic cholangiocarcinoma mouse model | 1. Activated CD4+ T cells and further enhanced the response and immune memory of CD8+ T cells 2. Inhibited tumor growth and improved the survival rate and OS |