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

The gp100:280-288 peptide presented by HLA-A*02:01 is a specific peptide-major histocompatibility complex (pMHC) target primarily utilized in the treatment of uveal and cutaneous melanoma (Nathan et al., 2021, NEJM). The peptide, derived from the melanocyte-specific protein PMEL (gp100), is processed and presented on the cell surface by the HLA-A*02:01 allele, making it a highly specific marker for cells of melanocytic origin (UniProt P17683). In healthy tissues, gp100 is involved in the formation of melanosomes, but its overexpression in melanoma cells makes it an ideal target for immunotherapy (NIH/NCI). Therapeutic strategies targeting this complex include bispecific T-cell engagers like tebentafusp, which bridges the pMHC on tumor cells with CD3 on T-cells to trigger an immune response (FDA Label: Kimmtrak). Additionally, various vaccines and TCR-engineered T-cell therapies have been developed to enhance the body's natural ability to recognize this specific antigen (PubMed: 15117006). Because gp100 is also expressed in normal melanocytes, safety concerns often involve inflammatory reactions in the skin, eyes, and ears (Middleton et al., 2020).

Other names

gp100(280-288)YLEPGPVTA peptidePMEL(280-288)gp100-HLA-A2 complexMelanocyte protein PMEL antigengp100:280-288

T-cell redirection via bispecific T-cell engagers (ImmTACs) or TCR-engineered T-cells to induce cytotoxic killing of melanoma cells expressing the specific pMHC complex.