Research ArticleImmunotherapy

Induction of Antigen-Specific Immunity with a Vaccine Targeting NY-ESO-1 to the Dendritic Cell Receptor DEC-205

Science Translational Medicine  16 Apr 2014:
Vol. 6, Issue 232, pp. 232ra51
DOI: 10.1126/scitranslmed.3008068

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Dendritic cells are the matchmakers of the immune system: They introduce T cells to antigen, providing the right context for the T cell to react. However, tumor alters the nearby microenvironment in such a way as to block immune activation. Dhodapkar et al. attempt to overcome this inhibition by targeting a tumor antigen directly to dendritic cells.

The authors tested a vaccine that consisted of a human antibody targeted to the dendritic cell receptor DEC-205 fused with the tumor antigen NY-ESO-1 in a cohort of patients with tumors refractory to other therapies. They also added Toll-like receptor ligands as adjuvants in a dose-escalating study. They found that treatment induced both humoral and cellular immunity in these patients, with no dose-limiting toxicities. What’s more, a subset of patients had either stable disease or disease regression, particularly those who had received immune checkpoint inhibitors. If these data can be reproduced in larger trials, this study suggests that targeting antigen to dendritic cells could be an additional avenue to boost the immune response to cancer.