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Trypanosoma cruzi as an effective cancer antigen delivery vector

Caroline Junqueira, Luara I. Santos, Bruno Galvão-Filho, Santuza M. Teixeira, Flávia G. Rodrigues, Wanderson D. DaRocha, Egler Chiari, Achim A. Jungbluth, Gerd Ritter, Sacha Gnjatic, Lloyd J. Old and Ricardo T. Gazzinelli
Proceedings of the National Academy of Sciences of the United States of America
Vol. 108, No. 49 (December 6, 2011), pp. 19695-19700
Stable URL: http://www.jstor.org/stable/23059557
Page Count: 6
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Abstract

One of the main challenges in cancer research is the development of vaccines that induce effective and long-lived protective immunity against tumors. Significant progress has been made in identifying members of the cancer testis antigen family as potential vaccine candidates. However, an ideal form for antigen delivery that induces robust and sustainable antigen-specific T-cell responses, and in particular of CD8+ T lymphocytes, remains to be developed. Here we report the use of a recombinant nonpathogenic clone of Trypanosoma cruzi as a vaccine vector to induce vigorous and longterm T cell-mediated immunity. The rationale for using the highly attenuated T. cruzi clone was (i) the ability of the parasite to persist in host tissues and therefore to induce a long-term antigen-specific immune response; (ii) the existence of intrinsic parasite agonists for Toll-like receptors and consequent induction of highly polarized T helper cell type 1 responses; and (iii) the parasite replication in the host cell cytoplasm, leading to direct antigen presentation through the endogenous pathway and consequent induction of antigenspecific CD8+ T cells. Importantly, we found that parasites expressing a cancer testis antigen (NY-ESO-1) were able to elicit human antigen-specific T-cell responses in vitro and solid protection against melanoma in a mouse model. Furthermore, in a therapeutic protocol, the parasites expressing NY-ESO-1 delayed the rate of tumor development in mice. We conclude that the T. cruzi vector is highly efficient in inducing T cell-mediated immunity and protection against cancer cells. More broadly, this strategy could be used to elicit a long-term T cell-mediated immunity and used for prophylaxis or therapy of chronic infectious diseases.

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