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SPD-gp100-CD40L is a recombinant fusion protein constructed by linking the spontaneously-multimerizing surfactant protein D (SPD) domain to the melanoma tumor antigen gp100 and the CD40 ligand (CD40L). This protein is designed to create a multitrimeric structure that simultaneously targets gp100 tumor antigen to dendritic cells (DCs) and provides strong activation signals via CD40L clustering, optimally activating the dendritic cells. Preclinical studies show SPD-gp100-CD40L is biologically active on dendritic cells, induces CD40-mediated NF-κB signaling, and, as a DNA vaccine (often combined with adjuvants such as IL-12p70 and GM-CSF plasmids), can enhance antigen presentation and promote anti-tumor immune responses in melanoma models. Expression of the components as separate molecules does not produce the same immunogenicity or tumor control, highlighting the importance of the fusion design[1][2][5].
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