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The development of cancer immunotherapy has long been a challenge. Here, we report that prophylactic vaccination with a highly attenuated Trypanosoma cruzi strain expressing NY-ESO-1 (CL-14-NY-ESO-1) induces both effector memory and effector CD8(+) T lymphocytes that efficiently prevent tumor development. However, the therapeutic effect of such a vaccine is limited. We also demonstrate that blockade of Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) during vaccination enhances the frequency of NY-ESO-1-specific effector CD8(+) T cells producing IFN-γ and promotes lymphocyte migration to the tumor infiltrate. As a result, therapy with CL-14-NY-ESO-1 together with anti-CTLA-4 is highly effective in controlling the development of an established melanoma.

Original publication

DOI

10.1007/s00262-014-1634-8

Type

Journal article

Journal

Cancer Immunol Immunother

Publication Date

03/2015

Volume

64

Pages

311 - 323

Keywords

Animals, Antigens, Neoplasm, CD8-Positive T-Lymphocytes, CTLA-4 Antigen, Cancer Vaccines, Female, Humans, Immunotherapy, Melanoma, Experimental, Membrane Proteins, Mice, Mice, Inbred C57BL, Recombinant Proteins, Trypanosoma cruzi