Alpha-fetoprotein (AFP) (AFP)

Alpha-fetoprotein (AFP) is a major fetal plasma protein produced by the yolk sac and the liver during embryonic development, serving as a structural and functional analog to serum albumin (UniProt: P02771). In healthy adults, the expression of AFP is transcriptionally repressed, but it is frequently reactivated and highly overexpressed in malignancies such as hepatocellular carcinoma (HCC) and non-seminomatous germ cell tumors (PubMed: 25236394). This restricted expression profile makes AFP an ideal tumor-associated antigen for targeted immunotherapy. Therapeutic approaches targeting AFP-expressing tumor cells primarily utilize antigen-specific CD8+ T cells and natural killer (NK) cells to induce tumor lysis. This is achieved through the development of TCR-engineered T cells, such as ADP-A2AFP, which recognize AFP peptides presented by HLA-A*02 on the tumor surface, or through cancer vaccines like ETBX-011 that stimulate an endogenous immune response (PubMed: 31534004). While AFP-targeted therapies show promise in treating advanced liver cancer, safety considerations include potential on-target off-tumor toxicity in cases of liver regeneration and the risk of cytokine release syndrome associated with potent T-cell activation (ClinicalTrials.gov: NCT03132792).

Other names

Alpha-1-fetoproteinAlpha-fetoglobulinHPAFPAFPDFETA

Engineered T-cell receptors (TCRs) or vaccine-induced T cells recognize AFP-derived peptides presented by HLA-A*02 on the surface of tumor cells, leading to direct cytotoxic killing by CD8+ T cells and indirect recruitment of NK cells (PubMed: 31534004, ClinicalTrials.gov: NCT03132792).