Inclusion body myositis (IBM)is an autoimmune condition in which cytotoxic T cells chronically attack muscle cells, leading to progressive weakness and severe disability Abcuro’s lead program, ABC008, is an anti-KLRG1 antibody capable of depleting highly differentiated cytotoxic T cells that … Read More
Development of immunotherapies for autoimmune diseases and cancer
KLRG1 – A Compelling Clinical Target in Immune Modulation
Abcuro is a clinical stage biotechnology company developing first-in-class immunotherapies for autoimmune diseases and cancer through precise modulation of effector cytotoxic T and NK cells. These cells can be specifically targeted as they express the receptor KLRG1 (killer cell lectin-like receptor G1).
In certain autoimmune diseases, KLRG1-expressing T cells are a major source of chronic tissue damage. In oncology, tumor cells that express E- or N- cadherin inhibit anti-tumor activity of T and NK cells because E- and N-cadherin bind to KLRG1 and KLRG1 functions as an immune checkpoint inhibitory receptor.
KLRG1 was identified as a compelling clinical therapeutic target through Abcuro’s bioinformatic analyses of clinical databases, as well as patient tissue and pathological immune cell transcriptome analyses.
KLRG1: One target, two mechanisms, multiple indications
KLRG1 is a transmembrane receptor. Itsligands are E- and N-cadherin,markers of epithelial and mesenchymal cells, respectively.
Unlike other targets for T cell depletion, KLRG1 expression is restricted to pathogenic, late-differentiated T and NK cells. These KLRG1+ cells are cytotoxic in both autoimmune diseases and in a broad range of cancers.
For patients with inclusion body myositis (IBM), muscle tissue is damaged by KLRG1+ cytotoxic T cells. In the tumor microenvironment, KLRG1 acts as an inhibitory immune checkpoint receptor, interacting with E- and N-cadherin to inhibit the anti-tumor activity of cytotoxic T and NK cells.
Abcuro co-founder Steven A Greenberg, MD and his collaborators have published results of studies on clinical samples in inclusion body myositis (IBM), titled “Highly Differentiated Cytotoxic T Cells in Inclusion Body Myositis”. IBM is an autoimmune disease characterized by T cell infiltration and attack … Read More