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

• DOI: 10.1007/s00262-014-1634-8
• Publication Date: 2014-11-21T16:53:22Z
• Authors: Luara Isabela dos...; Bruno Galvão-Filho; Paula Cristina de...; Caroline Junqueira; Miriam Santos Dutra; Santuza Maria Rib...; Maurício Martins ...; Gerd Ritter; Oliver Bannard; Douglas Thomas Fe...; Lis Ribeiro Anton...; Ricardo Tostes Ga...
• Keywords: CTLA-4

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.