Alpha-fetoprotein-derived peptide-MHC complex (AFP-pMHC)

Alpha-fetoprotein (AFP) is a 69 kDa glycoprotein primarily produced during fetal development by the liver and yolk sac, with levels dropping significantly after birth. In adults, its re-expression is a hallmark of hepatocellular carcinoma (HCC) and certain germ cell tumors, where it serves as a tumor-associated antigen (PMID: 11160744). AFP-derived peptides are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, such as HLA-A*02:01, forming a peptide-MHC (pMHC) complex (PMID: 10506494). This complex is a target for various immunotherapeutic strategies, including dendritic cell vaccines designed to prime the immune system, and T-cell receptor (TCR) engineered T-cells or TCR-like antibodies that directly recognize the pMHC on tumor cells (PMID: 12644402, PMID: 28104695). By targeting these specific epitopes, therapies aim to induce a potent and selective cytotoxic T-lymphocyte response against malignant cells while sparing healthy adult tissues that do not express AFP.

Other names

AFP peptide-HLA complexAFP-derived epitopesAFP-MHC complexAlpha-fetoprotein-derived peptides presented on MHCAFP-pHLA

The mechanism of action involves the specific recognition of the AFP peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-like antibodies. Upon binding, these therapeutic agents trigger a cytotoxic immune response, primarily through the activation of CD8+ T-cells, which release cytolytic granules such as perforin and granzymes to induce apoptosis in AFP-expressing tumor cells (PMID: 28104695, PMID: 30635454).