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

ABSTRACT

Introduction

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.

Areas covered

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.

Expert opinion

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.

KEYWORDS:

• LAG-3
• inhibitors
• cancer
• patents
• antibodies
• clinical trials

Article highlights

• Three approaches have been used for the development of LAG-3 inhibitors: inhibitory LAG-3 binding peptides, antagonist monoclonal and multispecific antibodies.

• There are more than one hundred clinical trials of 21 molecules that bind to LAG-3 and block its binding to MHC II.

• The approaches do not cover the development of peptides and small molecules that could inhibit the function of LAG-3.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded