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Melanocyte protein PMEL, commonly known as gp100, is a type I transmembrane glycoprotein essential for the maturation of melanosomes in melanocytes (UniProt: P40967). The specific peptide sequence spanning residues 280–288 (YLEPGPVTA) is a well-characterized tumor-associated antigen epitope that is processed and presented on the cell surface by the Human Leukocyte Antigen (HLA)-A*02:01 molecule (PMID: 9151713). This epitope is highly expressed in malignant melanoma, making it a primary target for immunotherapies such as peptide-based vaccines and T-cell receptor (TCR) bispecific therapies. For instance, tebentafusp is a bispecific protein that redirects T-cells to kill gp100-positive melanoma cells by binding this specific peptide-HLA complex (PMID: 34554117). While effective in targeting cancer, the expression of gp100 in normal melanocytes can lead to autoimmune-like side effects, most notably vitiligo, due to off-tumor, on-target activity (PMID: 11485911).
T-cell receptor (TCR) mediated activation and redirection of T-cells to tumor cells expressing the gp100 peptide-MHC complex (PMID: 34554117).
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