Table 7.
Emerging checkpoint inhibitors in preclinical and clinical trials.
| TIM-3 Preclinical Studies | |
|---|---|
| Study | Findings |
| Anti-TIM-3 blockade after PD-1 failure in lung cancer mice models [110] | OS: 11.9 weeks in TIM-3 blockade after PD-1 failure versus 5.0 weeks in PD-1 blockade monotherapy (p = 0.0008) in mice |
| PD-1 and TIM-3 expression in HBV-associated HCC versus cirrhosis [127] | Greater PD-1 expression in tumor tissue compared to surrounding cirrhosis tissue (p < 0.001) Greater TIM-3 expression in tumor tissue compared to cirrhosis tissue (p < 0.001) |
| LAG-3 Preclinical Studies | |
| Mechanisms of enhanced anti-tumor immunity with dual blockade of LAG-3 and PD-1 in an ovarian murine tumor model [133] | Increase in CD8+ T cells and decrease in Treg cells after blockade CD8+ T cells were not exhausted |
| Tumor response with LAG-3 and PD-1 blockade in Sa1N fibrosarcoma and MC38-colorectal adenocarcinoma [132] | Combination: tumor resolution (% population): Sa1N fibrosarcoma: 70% MC38-colorectal adenocarcinoma: 80% Monotherapy: tumor resolution PD-1 and LAG-3 monotherapy: 0–40% |
| Outcome of PD-L1 and LAG-3 expression in HCC [137] | Patients with high LAG-3 and PD-1 had poorer overall survival compared to elevation of only LAG-3 or PD-1 |
| TIGIT Preclinical Studies | |
| Mechanisms of resistance of anti-PD-1 blockade in mice liver tumor and effects of PD-1 and TIGIT blockade in mice liver tumor [143] | Anti-PD-1 blockade led to the mice harboring many more T cells expressing PD-1, LAG-3, and TIGIT compared to the non-treatment mice After anti-PD-1 anti-TIGIT blockade, there was evidence of reduced tumor growth, increased overall survival, and more expression of CD8+ T cells |
| Effect of TIGIT and PD-1 blockade on CD8+ T cells; CD8+ T cells effect on antibody response [144] | Dual blockade enhanced proliferation of CD8+ T cells compared to single blockade (p < 0.05) Tumors with CD8+ T cell depletion did not show response to anti-TIGIT and PD-L1 blockade |
| TIGIT expression of T cells in healthy donors compared to those with chronic HBV infection [147] | TIGIT expression was highest for effector T cells in chronic HBV infection compared to healthy donors |