Fibroblast activation protein alpha-derived peptide presented by human leukocyte antigen (FAP-HLA complex)

Fibroblast activation protein alpha (FAP) is a cell-surface serine protease that is significantly upregulated in cancer-associated fibroblasts (CAFs) across a wide range of solid tumors, including pancreatic, colorectal, and lung cancers. In the context of immunotherapy, FAP-derived peptides are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, specifically Human Leukocyte Antigen (HLA). This FAP-HLA complex acts as a tumor-stroma-specific antigen that can be recognized by T-cell receptors (TCRs). Targeting this complex allows for the selective destruction of CAFs, which play a critical role in promoting tumor growth, extracellular matrix remodeling, and immune evasion. Therapeutic strategies include TCR-engineered T cells and bispecific T-cell engagers designed to redirect the immune system against the tumor stroma. However, safety considerations are paramount as FAP is also expressed at low levels in certain healthy tissues, such as bone marrow-derived mesenchymal stem cells, potentially leading to off-tumor effects.

Other names

FAP-pMHCFAP peptide-MHC complexFAP-HLA-A*02 complexFibroblast activation protein alpha peptide-HLA-A2FAP-derived epitope

T-cell redirection and T-cell mediated cytotoxicity via T-cell receptor (TCR) recognition of the peptide-HLA complex on the surface of cancer-associated fibroblasts.