PMEL-derived peptide ITDQVPFSV presented by HLA-A*02:01 (gp100:209-217/HLA-A*02:01)

The PMEL-derived peptide ITDQVPFSV presented by HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) target primarily utilized in the immunotherapy of melanoma. PMEL, also known as gp100, is a lineage-specific glycoprotein involved in the formation of melanosomes and is highly expressed in both cutaneous and uveal melanoma cells. The ITDQVPFSV sequence corresponds to amino acids 209-217 of the gp100 protein and is processed and presented on the cell surface by the HLA-A*02:01 molecule, the most common MHC class I allele in Caucasian populations. This specific pMHC complex serves as a critical recognition site for T-cell receptors (TCRs), making it a prime target for various therapeutic modalities including bispecific TCR-fusion proteins, peptide vaccines, and adoptive cell therapies. Tebentafusp, a first-in-class ImmTAC (Immune mobilizing monoclonal TCR Against Cancer), specifically targets this complex to redirect T-cells to kill melanoma cells. While effective, targeting this complex can lead to on-target off-tumor toxicities due to the presence of PMEL in healthy melanocytes, resulting in side effects such as skin rash, vitiligo, and ocular inflammation.

Other names

gp100 peptide 209-217g209 peptideMelanocyte protein PMEL peptide ITDQVPFSVHLA-A*02:01/gp100(209-217) complexGlycoprotein 100 (gp100) antigen

T-cell redirection via bispecific T-cell engagers (BiTEs) or ImmTACs; active immunization to induce peptide-specific CD8+ T-cells; adoptive transfer of TCR-engineered T-cells.