Trypanosoma cruzias an effective cancer antigen delivery vector

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.cytokine | prophylaxis | protozoa | innate immunity | Trypanosoma cruzi CL-14

Trypanosoma cruzi extracts elicit protective immune response against chemically induced colon and mammary cancers

“…Nonpathogenic live parasites, such as Leishmania tarentolae , T. gondii and T. cruzi are emerging as novel candidates for gene delivery in anticancer therapeutic approaches . In fact, it was found that a recombinant nonpathogenic clone of T. cruzi expressing a cancer testis antigen (NY‐ESO‐1) induces antigen‐specific T‐cell responses and effective protection against tumors in a mouse model . The use of T. cruzi ‐derived TLR agonists as immunological adjuvants also resulted in a significant delay in the growth of the B16‐F10 melanoma cell line expressing NY‐ESO‐1 antigen .…”

Parasite Infection, Carcinogenesis and Human Malignancy

“…Further to the anticancer properties, T. cruzi is an effective cancer antigen delivery vector (Junqueira et al, 2011). A study utilized the attenuated T. cruzi CL-14 clone to express exogenously a cancer testis antigen (NY-ESO-1) and showed that T. cruzi parasites expressing NY-ESO-1 were able to induce strong NY-ESO-1 specific immune responses both in-vitro and in-vivo .…”

“…A study utilized the attenuated T. cruzi CL-14 clone to express exogenously a cancer testis antigen (NY-ESO-1) and showed that T. cruzi parasites expressing NY-ESO-1 were able to induce strong NY-ESO-1 specific immune responses both in-vitro and in-vivo . Interestingly, immunization with T. cruzi parasites expressing NY-ESO-1 would lead to an effective immune response to kill tumor cells and to inhibit tumor development (Junqueira et al, 2011). Taken together, T. cruzi may exert both carcinogenic and antitumor effects (Fig.…”

A non-pathogenic live vector as an efficient delivery system in vaccine design for the prevention of HPV16 E7-overexpressing cancers

“…Recently, a recombinant non-pathogenic clone of Trypanosoma cruzi expressing a cancer testis antigen (NY-ESO-1) has been used as a vaccine vector to induce long-term T cell-mediated immunity and delay the rate of tumor development in mice (Junqueira et al, 2011).…”