Dendritic Cell Targeting of Survivin Protein in a Xenogeneic Form Elicits Strong CD4 super(+) T Cell Immunity to Mouse Survivin

• Published in: Journal of Immunology Vol. 177; no. 12; pp. 8410 - 8421
• Main Authors: Charalambous, Anna, Oks, Margarita, Nchinda, Godwin, Yamazaki, Sayuri, Steinman, Ralph M
• Format: Journal Article
• Language: English
• Published: 01.12.2006
• ISSN: 0022-1767; 1365-2567

To determine whether strong CD4 super(+) T cell immunity could be induced to a nonmutated self protein that is important for tumorigenesis, we selectively targeted the xenogeneic form of survivin, a survival protein overexpressed in tumors, to maturing dendritic cells in lymphoid tissues. Dendritic cell targeting via the DEC205 receptor in the presence of anti-CD40 and poly(I:C) as maturation stimuli, induced strong human and mouse survivin-specific CD4 super(+) T cell responses, as determined by IFN- gamma , TNF- alpha , and IL-2 production, as well as the development of lytic MHC class II-restricted T cells and memory. Immunity was enhanced further by depletion of CD25 super(+)foxp3 super(+) cells before vaccination. anti-DEC205-human survivin was superior in inducing CD4 super(+) T cell responses relative to other approaches involving survivin plasmid DNA or survivin peptides with adjuvants. However, we were unable to induce CD8 super(+) T cell immunity to survivin by two doses of DEC205-targeted survivin or the other strategies. Therefore, significant CD4 super(+) T cell immunity to a self protein that is overexpressed in most human cancers can be induced by DEC205 targeting of the Ag in its xenogeneic form to maturing DCs.