Blockade of CTLA-4 promotes the development of effector CD8 super(+) T lymphocytes and the therapeutic effect of vaccination with an attenuated protozoan expressing NY-ESO-1

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 super(+) T lymphocytes that efficiently prevent tumor...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2015-03, Vol.64 (3), p.311-323
Main Authors: Santos, Luara Isabela, Galvao-Filho, Bruno, Faria, Paula Cristina, Junqueira, Caroline, Dutra, Miriam Santos, Teixeira, Santuza Maria Ribeiro, Rodrigues, Mauricio Martins, Ritter, Gerd, Bannard, Oliver, Fearon, Douglas Thomas, Antonelli, Lis Ribeiro, Gazzinelli, Ricardo Tostes
Format: Article
Language:English
Subjects:
Trypanosoma cruzi
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Summary: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 super(+) 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 super(+) T cells producing IFN- gamma 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.
ISSN:0340-7004
1432-0851
DOI:10.1007/s00262-014-1634-8