Melanocyte protein PMEL (gp100) peptide 280-288 presented by HLA-A*02:01 (gp100:280-288/HLA-A*02:01)

The target consists of a specific 9-amino acid peptide (YLEPGPVTA) derived from the melanocyte protein PMEL (also known as gp100) presented on the cell surface by the Human Leukocyte Antigen (HLA) allele A*02:01. PMEL is a transmembrane glycoprotein essential for the structural organization of melanosomes, where melanin is synthesized. While expressed in normal melanocytes, it is significantly overexpressed in most melanoma cells, making it a prime candidate for immunotherapy. The gp100:280-288 epitope is a well-characterized immunodominant peptide that can be recognized by the T-cell receptor (TCR) of cytotoxic T lymphocytes. Therapeutic strategies targeting this complex include the bispecific TCR-anti-CD3 fusion protein tebentafusp, which redirects T cells to kill gp100-expressing tumor cells. Because PMEL is also expressed in healthy melanocytes, treatment can lead to on-target off-tumor effects such as vitiligo or skin rashes. This target is particularly significant in the treatment of uveal melanoma, where it has been successfully utilized to improve overall survival in HLA-A*02:01-positive patients.

Other names

gp100:280-288YLEPGPVTA peptidePMEL17SILVMelanocyte-specific lineage antigen gp100HLA-A*02:01/gp100(280-288) complex

T-cell redirection via bispecific T-cell engagers (ImmTACs) or direct T-cell receptor (TCR) recognition to induce cytotoxic lysis of tumor cells.