T cell receptor specific for Folate receptor alpha (FRα) (FRα-specific TCR)

The T cell receptor (TCR) on FRα-specific CD4+ T cells is a heterodimeric surface protein complex that specifically recognizes peptides derived from Folate Receptor alpha (FRα) presented by Major Histocompatibility Complex (MHC) Class II molecules (Knutson et al., 2006, Journal of Clinical Oncology). FRα, also known as FOLR1, is a tumor-associated antigen highly overexpressed in ovarian, breast, and lung cancers, making it a prime candidate for immunotherapy (Parker et al., 2005, Analytical Biochemistry). CD4+ T cells bearing these TCRs are essential for orchestrating an effective anti-tumor response through the secretion of Th1 cytokines like IFN-gamma and TNF-alpha (Disis et al., 2014, Vaccine). These cytokines not only inhibit tumor growth directly but also activate other immune effectors, such as cytotoxic CD8+ T cells and macrophages. Therapeutic strategies leveraging this target include multi-epitope vaccines like TPIV200, which aim to expand the endogenous population of FRα-specific CD4+ T cells in cancer patients (ClinicalTrials.gov, NCT01606241). Additionally, TCR-engineered T cell (TCR-T) therapies are being developed to provide patients with high-affinity T cells capable of recognizing FRα-positive tumor cells. Monitoring the frequency and functional status of these TCRs serves as a vital biomarker for assessing the immunogenicity and clinical efficacy of FRα-targeted treatments. Safety considerations for therapies involving these TCRs include potential on-target, off-tumor toxicity and the risk of cytokine release syndrome (CRS) following T cell activation.

Other names

Folate receptor alpha-specific T-cell receptorFR-alpha-specific TCRFRα-TCRFOLR1-specific TCRFolate receptor alpha-specific CD4+ T-cell receptor

Activation of CD4+ T cells via recognition of FRα peptides on MHC Class II, leading to Th1-mediated anti-tumor immunity.