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

Dos Santos, L. I., Galvao-Filho, B., de Faria, P. C., Junqueira, C., Dutra, M. S., Teixeira, S. M., Rodrigues, M. M., Ritter, G., Bannard, O., Fearon, D. T., Antonelli, L. R., Gazzinelli, R. T. (March 2015) 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. Cancer Immunol Immunother, 64 (3). pp. 311-23. ISSN 0340-7004

URL: http://www.ncbi.nlm.nih.gov/pubmed/25403749
DOI: 10.1007/s00262-014-1634-8

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.

Item Type: Paper
Uncontrolled Keywords: Animals Antigens, Neoplasm/administration & dosage/genetics/*immunology CD8-Positive T-Lymphocytes/*immunology/parasitology CTLA-4 Antigen/antagonists & inhibitors/*immunology Cancer Vaccines/*immunology Female Humans Immunotherapy/*methods Melanoma, Experimental/immunology/parasitology/*therapy Membrane Proteins/administration & dosage/genetics/*immunology Mice Mice, Inbred C57BL Recombinant Proteins/administration & dosage/genetics/immunology Trypanosoma cruzi/genetics/immunology
Subjects: diseases & disorders > cancer
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells
CSHL Authors:
Communities: CSHL Cancer Center Program > Signal Transduction
CSHL labs > Fearon lab
Depositing User: Matt Covey
Date: March 2015
Date Deposited: 15 Oct 2015 20:37
Last Modified: 15 Oct 2015 20:37
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31928

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving