Document Type

Article

Publication Date

2006

Keywords

antigen specificity, CD4+ T lymphocyte, cytokine production, memory T lymphocyte, dendritic cell, T cell depletion

Abstract

To determine whether strong CD4+ T cell immunity could be induced to a nonmutated self protein that is important for tumorigenesis, we selectively targeted the xenogencic 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+ T cell responses, as determined by IFN-γ, TNF-α, 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+foxp3+ cells before vaccination. anti-DEC205-human survivin was superior in inducing CD4+ T cell responses relative to other approaches involving survivin plasmid DNA or survival peptides with adjuvants. However, we were unable to induce CD8 + T cell immunity to survivin by two doses of DEC205-targeted survivin or the other strategies. Therefore, significant CD4+ 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.

Comments

Open Access

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