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LAG-3 is considered to be the third point of immunological control in relation to clinical trials that address cancer treatment, only behind PD-1 and CTLA-4, due to its role as a suppressor of the immune response and enhancer of differentiation of Treg cells. The authors focus on emphasizing the strategy of development of LAG-3 inhibitors to develop anticancer therapeutics, especially from the perspective of designing new monoclonal and bispecific antibodies against LAG-3. This article also covers details of patents and clinical trials of LAG-3 inhibitors reported in the literature. In addition, we highlight as future research challenges the design and development of peptides and small molecules as inhibitors of LAG-3 function. Three approaches have been used for the development of LAG-3 inhibitors, and they include inhibitory LAG-3 binding peptides and antagonist monoclonal and multispecific antibodies. These approaches include more than 100 clinical trials of 21 molecules that bind to LAG-3 and block its binding to MHC II. However, these approaches do not cover the design and development of peptides and small molecules that could inhibit the function of LAG-3, for which it is necessary to develop new alternatives that cover this gap.

Approaches for development of LAG-3 inhibitors and the promise they hold as anticancer agents