Emerging new immune checkpoint inhibitors in solid tumor immunotherapy

Abstract

The advent of immune checkpoint inhibitors (ICIs) has revolutionised cancer therapy and has led to improved outcomes for patients with many cancers. While proven inhibitors targeting programmed cell death protein 1 (PD- 1), programmed cell death ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated protein 4 (CTLA- 4) have had great success, new ICIs are on the horizon. However, data from clinical trials indicate that some patients develop resistance to ICIs targeting PD- 1/L1 and/or CTLA- 4 for multiple mechanisms. This gives rise to the idea that combining therapy by using multiple ICIs could help overcome this resistance through the inhibition of multiple pathways and immune checkpoints. Therefore, the new generation of immune checkpoint inhibitors opens up new therapeutic candidates for solid tumors. This review covers novel checkpoint agents, including T cell immunoglobulin and mucin domain 3 (TIM- 3), lymphocyte activating gene 3 (LAG- 3), and other promising pathways, including Ig V domain suppressor for T cell activation (VISTA). We review the underlying mechanisms of these targets, how they have been developed in the laboratory and clinic, and the initial efficacy and safety seen in ongoing trials. We also discuss combination strategies to further improve their therapeutic potential. By identifying challenges and opportunities with these new agents, this review explores the direction in which immunotherapy for solid tumors is headed and calls for further research in this emerging field.

Keywords: Immunotherapy; LAG- 3; Solid tumors; TIM- 3; VISTA.