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Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2014 Apr 07; Vol. 211 (4), pp. 715-25. Date of Electronic Publication: 2014 Mar 31. - Publication Year :
- 2014
-
Abstract
- Cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade with a monoclonal antibody yields durable responses in a subset of cancer patients and has been approved by the FDA as a standard therapy for late-stage melanoma. We recently identified inducible co-stimulator (ICOS) as a crucial player in the antitumor effects of CTLA-4 blockade. We now show that concomitant CTLA-4 blockade and ICOS engagement by tumor cell vaccines engineered to express ICOS ligand enhanced antitumor immune responses in both quantity and quality and significantly improved rejection of established melanoma and prostate cancer in mice. This study provides strong support for the development of combinatorial therapies incorporating anti-CTLA-4 and ICOS engagement.
- Subjects :
- Animals
Antibodies, Monoclonal pharmacology
Antibodies, Monoclonal therapeutic use
Antigen Presentation drug effects
CD4-Positive T-Lymphocytes drug effects
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes drug effects
CD8-Positive T-Lymphocytes immunology
CTLA-4 Antigen metabolism
Cancer Vaccines immunology
Cytokines biosynthesis
Disease Models, Animal
Immunologic Memory drug effects
Immunosuppression Therapy
Ligands
Lymphocytes, Tumor-Infiltrating drug effects
Lymphocytes, Tumor-Infiltrating immunology
Male
Melanoma, Experimental immunology
Melanoma, Experimental pathology
Mice
Prostatic Neoplasms immunology
Prostatic Neoplasms prevention & control
Signal Transduction drug effects
Signal Transduction immunology
Up-Regulation drug effects
CTLA-4 Antigen antagonists & inhibitors
Immunotherapy
Inducible T-Cell Co-Stimulator Protein metabolism
Melanoma, Experimental drug therapy
Prostatic Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 211
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 24687957
- Full Text :
- https://doi.org/10.1084/jem.20130590