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

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

Author Santos, Luara Isabela dos Google Scholar
Galvao-Filho, Bruno Google Scholar
Faria, Paula Cristina de Google Scholar
Junqueira, Caroline Google Scholar
Dutra, Miriam Santos Google Scholar
Ribeiro Teixeira, Santuza Maria Google Scholar
Rodrigues, Mauricio Martins Autor UNIFESP Google Scholar
Ritter, Gerd Google Scholar
Bannard, Oliver Google Scholar
Fearon, Douglas Thomas Google Scholar
Antonelli, Lis Ribeiro Google Scholar
Gazzinelli, Ricardo Tostes Google Scholar
Institution Fundacao Oswaldo Cruz
Universidade Federal de Minas Gerais (UFMG)
Universidade Federal de São Paulo (UNIFESP)
Mem Sloan Kettering Canc Ctr
Univ Calif San Francisco
Univ Cambridge
Univ Massachusetts
Abstract 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-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.
Keywords Cancer
Immunotherapy
NY-ESO-1
Anti-CTLA-4
Trypanosoma cruzi
Language English
Sponsor Atlantic Philanthropies/Program of Clinical Discoveries from the LICR
Fundacao de Amparo a Pesquisa de Minas Gerais
Fundacao Oswaldo Cruz
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2015-03-01
Published in Cancer Immunology Immunotherapy. New York: Springer, v. 64, n. 3, p. 311-323, 2015.
ISSN 0340-7004 (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 311-323
Origin http://dx.doi.org/10.1007/s00262-014-1634-8
Access rights Closed access
Type Article
Web of Science ID WOS:000350351200005
URI http://repositorio.unifesp.br/handle/11600/38810

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