A successful cancer vaccine needs to overcome the effects of immune-suppressor cells such as Treg lymphocytes, suppressive cytokine-secreting Tr1 cells, and myeloid-derived suppressor cells (MDSCs), while enhancing tumor-specific immune responses. Given the relative poor efficacy associated with current cancer vaccines, a novel vaccine platform called (DPX) was developed. C3 tumor-challenged mice were immunized with HPV-E7 peptide in DPX- or conventional-emulsion- (CE-) based vaccine. While control mice showed marked increase in Treg/MDSCs in spleen and blood, in mice treated with DPX-E7 the levels remained similar to tumor-free naive mice. Such differences were also seen within the tumor. Antigen-specific IL10-secreting CD4/CD8 T cells and TGF-β +CD8+ T cell frequencies were increased significantly in CE-treated and control mice in contrast to DPX-E7-immunized mice. Analysis of tumor-infiltrating cells revealed higher frequency of suppressor cells in untreated controls than in DPX-E7 group while the converse was true for tumor-infiltrating CD8 T cells. Immunization of tumor-bearing HLA-A2 transgenic mice with human vaccine DPX-0907, a peptide-based vaccine for breast/ovarian/prostate cancers, showed efficient induction of immune response to cancer peptides despite the presence of suppressor cells. Thus, this study provides the rationale for using DPX-based cancer vaccines in immune-suppressed cancer patients, to induce effective anticancer immunity. 1. Introduction Lack of effective cancer treatments and the emergence of drug resistance in progressively growing tumors make cancer immunotherapy a viable alternative to treat and manage metastatic diseases [1]. Synthetic peptide-based vaccines that are capable of inducing specific T cell-mediated immunity are emerging as attractive therapeutic strategies for cancers. While such vaccines have proven rather effective in diverse animal studies, multiple human clinical trials implementing this approach have thus far yielded limited success [2–5]. Although many of these trials were able to elicit significant number of tumor antigen-specific T cells in cancer patients, clinical regressions of disease remain rare [6]. Although incompletely understood, the lack of clinical efficacy for peptide-based vaccines may be related to several factors such as poor immunogenicity of the chosen peptides, insufficient numbers or appropriate functional polarity of responder T cells, inefficient trafficking of effector cells into tumor microenvironment, and, more importantly, tumor-induced increase in the number of
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