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Glycoprotein 100 (gp100, also called Pmel, Pmel17, or Silver protein) is a melanosome-specific transmembrane glycoprotein essential for the formation of fibrillar scaffolds in melanosomes, facilitating melanin deposition. It is expressed primarily in melanocytes and the majority of melanomas, making it a specific and attractive target for immunotherapy. gp100 functions both in melanosome biogenesis and as a tumor-associated antigen, presented by MHC class I and II molecules for immune recognition. Therapeutic approaches targeting gp100 include bispecific T cell engagers (e.g., Tebentafusp), vaccine peptides, and adoptive cell transfer. The clinical efficacy of these agents relies on the presence and level of gp100 expression in tumor cells, with safety concerns arising from its expression in healthy melanocytes. Variable expression among patients provides a rationale for biomarker-based patient stratification.
T cell recruitment/engagement via HLA-presented gp100 peptide (e.g., Tebentafusp); Immune recognition and cytolysis of gp100-positive melanoma cells by CD8+ and CD4+ T cells; Vaccine-induced T cell response against gp100 epitopes
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