Transmembrane 4 L6 family member 1 (TM4SF1)

Transmembrane 4 L6 family member 1 (TM4SF1) is a small plasma membrane glycoprotein belonging to the L6 superfamily of tetraspanin-like proteins (UniProt P30408). It is significantly overexpressed in a wide range of solid tumors, including non-small cell lung, breast, and pancreatic cancers (PMID: 29158510). The protein is also notably found on the vascular endothelium of the tumor microenvironment, distinguishing it from many other tumor antigens. Biologically, TM4SF1 functions as a key regulator of cell motility, proliferation, and angiogenesis by interacting with integrins and modulating growth factor signaling pathways like VEGF (PMID: 30030315). Its dual presence on both malignant cells and tumor-associated vasculature makes it an exceptionally attractive target for cancer therapy. Therapeutic strategies currently under investigation include antibody-drug conjugates (ADCs), such as vobasertamab mafodotin (PF-06647020), which has been evaluated in clinical trials (NCT02252211). Additionally, TM4SF1-targeted CAR-T cell therapies are being explored to leverage its high expression in various carcinomas. Clinical challenges include managing potential off-target effects, as low levels of TM4SF1 expression are observed in some normal tissues like the lung and skin. Despite these challenges, its role in promoting tumor progression and metastasis continues to drive interest in TM4SF1 as a diagnostic and therapeutic focal point.

Other names

L6M3S1TAAL6Transmembrane 4 superfamily member 1Tumor-associated antigen L6

Antibody-drug conjugate (ADC) mediated delivery of cytotoxic agents and CAR-T cell mediated direct tumor cell lysis