HLA-A*02:01-restricted Folate Binding Protein peptide complex (HLA-A2/FBP)

The HLA-A2 presenting FBP-derived peptide complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a target for cancer immunotherapy. Folate Binding Protein (FBP), also known as Folate Receptor alpha (FRα), is a cell-surface glycoprotein that is highly overexpressed in several epithelial malignancies, including ovarian, breast, and lung cancers, while maintaining very low expression in most normal tissues (Sears et al., 2011, PubMed: 21149658). Intracellular processing of FBP leads to the generation of specific peptides, most notably the immunodominant E39 epitope (EIWTHSYKV), which are presented on the cell surface by the HLA-A*02:01 allele (Kim et al., 1999, PubMed: 10449132). This complex is recognized by the T-cell receptors (TCRs) of CD8+ cytotoxic T lymphocytes, triggering an immune response against the tumor cells. Therapeutic approaches targeting this complex include peptide-based vaccines, such as E39 and its modified version E39', which aim to elicit a robust and durable T-cell response in patients (NCT01580696, ClinicalTrials.gov). Additionally, this pMHC complex is a candidate for advanced modalities like TCR-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers. The high tumor-to-normal tissue expression ratio of FBP makes this complex an attractive target for minimizing off-target effects, though monitoring for potential toxicity in tissues with low-level FBP expression remains necessary.

Other names

HLA-A2/FBP peptide complexHLA-A*02:01/FR-alpha peptide complexE39-HLA-A2 complexFBP-derived peptide-MHC complexFolate Receptor alpha peptide-HLA-A2 complex

Induction of peptide-specific CD8+ cytotoxic T lymphocyte (CTL) response against tumor cells presenting the FBP-derived peptide on HLA-A2.