LIGHT Immune Checkpoint Molecule for Drug Development
Immune Checkpoint LIGHT
LIGHT, also known as TNFSF14 or CD258, is a member of the tumor necrosis factor (TNF) ligand superfamily, which is always involved in the regulation of cell survival and proliferation as well as innate and adaptive immune responses.
Activated T and B lymphocytes, natural killer (NK) cells, immature dendritic cells, granulocytes, and monocyte/macrophages
Structure of LIGHT
There are three forms of LIGHT protein, which include the full-length type 2 transmembrane glycoprotein with 240 amino acid residues and relative molecular weight of 29 kda, a non-glycosylated protein composed of 204 amino acid residues that lack a transmembrane region and only activates T lymphocytes, as well as the membrane-anchored homotrimeric complex on the cell surface.
Expression of LIGHT
LIGHT is widely expressed on activated T and B lymphocytes, natural killer (NK) cells, immature dendritic cells, granulocytes, and monocyte/macrophages.
Function of LIGHT
LIGHT interacts with three types of receptors, which include herpesvirus entry mediator (HVEM), lymphotoxin β receptor (LTβR), and decoy receptor 3 (DcR3; also named as TNFRSF6B). HVEM and LTβR mediate LIGHT-induced T cell co-stimulation and subsequent cytokine production. As a soluble receptor without a TMD, DcR3 works as a competitive inhibitor of LIGHT-induced cellular responses.
Fig.1 Structure of LIGHT.
Preclinical and Clinical Development of Drugs Targeting LIGHT
Some studies have shown that high expression of LIGHT in tumor tissues can induce the accumulation and activity of tumor-specific T lymphocytes at tumor sites, improve the immune microenvironment of tumor tissues, and inhibit a variety of tumor cell lines. Besides, the expression of LIGHT can not only inhibit the growth of primary tumors but also inhibit tumor metastasis and promote apoptosis of metastatic tumor cells. LIGHT-HVEM and LIGHT-LTβR pathways present the dual effect of promoting and inhibiting tumor growth. According to the specific monoclonal antibodies or siRNA and other biotechnology, LIGHT-mediated signaling pathways or specific molecular binding targets are regulated to improve the biological activity of LIGHT. Now, several LIGHT-targeting therapeutics are currently in early phase clinical trials.
Services at Creative Biolabs
Creative Biolabs has been a long-term expert in the field of immune checkpoints drug discovery. Now we can provide a series of services, including but not limited to: