Hepatitis A virus cellular receptor 2 (TIM-3) (TIM-3)

Hepatitis A virus cellular receptor 2 (TIM-3), also known as T-cell immunoglobulin and mucin-domain containing-3, is a type I transmembrane protein that serves as a critical inhibitory checkpoint receptor on T cells, NK cells, and myeloid cells (UniProt Q8TDQ0). It is primarily known for its role in inducing T-cell exhaustion and limiting Th1-mediated immune responses, particularly in the tumor microenvironment (PubMed: 30104445). In the specific context of Chimeric Antigen Receptor (CAR) T-cell therapy, TIM-3 is frequently upregulated following chronic antigen stimulation, serving as a hallmark of CAR T-cell dysfunction and reduced persistence (PubMed: 31092554). Therapeutic strategies targeting TIM-3 include the use of monoclonal antibodies like Sabatolimab or the genetic deletion of the HAVCR2 gene in CAR T cells to enhance their metabolic fitness and anti-tumor efficacy (PubMed: 33616316). TIM-3 interacts with several ligands, including Galectin-9, Phosphatidylserine, HMGB1, and CEACAM1, to mediate its suppressive signals (PubMed: 26231121).

Other names

Hepatitis A virus cellular receptor 2HAVCR2TIMD3CD366T-cell membrane protein 3

Immune checkpoint inhibition via antagonism of the TIM-3 receptor to prevent T-cell exhaustion and restore anti-tumor activity.