Cytotoxic T lymphocyte antigen-4 and immune checkpoint blockade

The relationship between cancer and the immune system is complex and provides unique therapeutic opportunities. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a regulatory molecule that suppresses T cell effector function following initial activation by costimulatory signals. Fully human monoclonal an...

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Bibliographic Details
Published in:The Journal of clinical investigation 2015-09, Vol.125 (9), p.3377-3383
Main Authors: Buchbinder, Elizabeth, Hodi, F Stephen
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal - therapeutic use
Antigen receptors, T cell
Antigens
Biomedical research
Cancer
Care and treatment
Cell Cycle Checkpoints - drug effects
Cell Cycle Checkpoints - immunology
Cell growth
CTLA-4 Antigen - antagonists & inhibitors
CTLA-4 Antigen - immunology
Cytotoxicity
Dendritic cells
Genetic aspects
Health aspects
Humans
Immune response
Immune system
Immunoglobulins
Immunotherapy
Lymphocytes
Medical prognosis
Melanoma
Melanoma - immunology
Melanoma - pathology
Melanoma - therapy
Metastasis
Neoplasm Metastasis
Receptors
Review Series
T cell receptors
T cells
T-Lymphocytes, Cytotoxic - immunology
T-Lymphocytes, Cytotoxic - pathology
Tumors
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Summary:The relationship between cancer and the immune system is complex and provides unique therapeutic opportunities. Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a regulatory molecule that suppresses T cell effector function following initial activation by costimulatory signals. Fully human monoclonal antibodies targeting CTLA-4 have been shown to increase T cell function and antitumor responses in patients with advanced metastatic melanoma. Responses observed with such immune checkpoint therapy can follow a different pattern from that seen with cytotoxic chemotherapy or targeted therapy and may continue after therapy is discontinued. In addition, the toxicities that are associated with anti-CTLA-4 therapy may differ from those of conventional therapies and consist of inflammatory events in parts of the body that do not contain cancerous cells. Early recognition of these inflammatory events and intervention is important, and the identification of predictive biomarkers continues to be an unfulfilled need in the field of immunotherapy. Combinatorial approaches with targeted therapies, radiation therapy, chemotherapy, or other immune checkpoint agonists/antagonists have the potential to increase the efficacy of CTLA-4 blockade.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI80012