Next-IO™ LAG-3 x CTLA-4

The goal of this study is to develop LAG-3 x CTLA-4 therapeutic bispecific antibody, for use in colorectal cancer immunotherapy.

T cells that have infiltrated tumors and expressed the checkpoint receptor CTLA-4 in large quantities, particularly T regulatory cells (Tregs).

LAG-3 belongs to the immunoglobulin superfamily (IgSF), which Treg overexpress in the TME, where they inhibit the proliferation and activation of T cells.

A new antibody known as a bispecific antibody (BsAb) targets two distinct antigens and preferentially reroutes effector cells to target cells, therefore mediating specific death. This improved synergistic anti-tumor effect demonstrates a potentially effective immunotherapy strategy.

With its dual checkpoint blocking approach, our initiative aims to target CTLA-4 and LAG-3 concurrently, potentially enhancing T cell activation and proliferation and offering hope for anti-tumor T cell immunity.

One of the IgSF’s type I transmembrane proteins is LAG-3. It functions to adversely regulate the homeostasis of activated T cells, natural killer cells, or B cells. These cells express it most frequently. The next generation of immunological checkpoint proteins, known as LAG-3, has been found to have several functions in cancer immunity, such as:

reduction in the production of interleukin (IL), interferon-gamma, and tumor necrosis factor in T cells, as well as inhibition of Th1 cell proliferation.

The TCR signal is inhibited by the interaction of LAG-3 with MHC-II, which stops the same MHC molecule from binding to both TCR and CD4.

Crosslinking of LAG-3 and CD3/TCR complexes can affect T cell proliferation, cytokine production, and calcium flow.

In addition to other immunological checkpoints, LAG-3 prevents T cell activation, particularly PD-1.

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