Abstract
<div>Abstract<p>Stimulation of tumor-specific responses in both CD4<sup>+</sup> and CD8<sup>+</sup> T cells has been a challenge for effective tumor vaccines. We designed a vaccine vector containing the AIDA-1 autotransporter and DNA vaccine elements, generating a murine melanoma vaccine that was delivered by the attenuated <i>Salmonella</i> strain SL7207. Growth of murine subcutaneous melanoma was significantly inhibited by intranasal immunization with the <i>Salmonella</i> tumor vaccine. The vaccine activated tumor-specific CD4<sup>+</sup> and CD8<sup>+</sup> T-cell responses, with increased T-cell proliferation, tumor antigen–specific Th1 cytokine production, increased percentages of tetramer positive cells, and cytotoxicity. CD4<sup>+</sup> or CD8<sup>+</sup> T-cell depletion resulted in the loss of antitumor activity of the <i>Salmonella</i> tumor vaccine, suggesting that the efficacy of the vaccine was dependent on both CD4<sup>+</sup> and CD8<sup>+</sup> T cells. Lung metastasis of the tumor was also inhibited by vaccine treatment. Similarly, the percentages of tumor-specific Th1 cytokine production by CD4<sup>+</sup> and CD8<sup>+</sup> T cells in the spleen, tumor, and bronchoalveolar lavage were increased after vaccine treatment. Tumor-specific proliferation of CD4<sup>+</sup> and CD8<sup>+</sup> T cells was also promoted by the vaccine. Tetramer staining and cytotoxicity assay showed enhanced tumor-specific CD8<sup>+</sup> T-cell response after vaccine treatment. Therefore, the <i>Salmonella</i> tumor vaccine could activate both tumor-specific CD4<sup>+</sup> and CD8<sup>+</sup> T-cell responses. This vaccine strategy may be widely applicable to the development of oral or nasal vaccines against tumors. <i>Cancer Immunol Res; 5(6); 503–14. ©2017 AACR</i>.</p></div>
Published Version
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