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gp100 DNA vaccine is a plasmid-based DNA immunotherapy designed to treat melanoma by inducing an immune response against the melanocyte protein PMEL, also known as gp100. gp100 is a membrane-associated glycoprotein involved in melanosome maturation and is highly expressed in the majority of malignant melanomas. The vaccine typically consists of a DNA plasmid (such as the pUMVC3 vector) encoding the human gp100 sequence. Upon intramuscular or intradermal administration—frequently facilitated by electroporation to enhance cellular uptake—host cells take up the plasmid and express the gp100 protein. This intracellular production allows the protein to be processed and presented via the MHC Class I and Class II pathways, thereby activating both CD8+ cytotoxic T lymphocytes and CD4+ helper T cells specific for gp100 epitopes. This targeted immune activation aims to overcome peripheral tolerance and eradicate gp100-positive tumor cells. Clinical development has primarily focused on its use in patients with advanced or metastatic melanoma, often in combination with systemic cytokines like Interleukin-2 or immune checkpoint inhibitors to enhance the magnitude and duration of the antitumor T-cell response.
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