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Overcoming Tumor-Induced Immune Suppression: From Relieving Inhibition to Providing Costimulation with T Cell Agonists.
- Source :
-
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy [BioDrugs] 2018 Jun; Vol. 32 (3), pp. 221-231. - Publication Year :
- 2018
-
Abstract
- Recent advancements in T-cell biology and antibody engineering have opened doors to significant improvements in cancer immunotherapy. Initial success with monoclonal antibodies targeting key receptors that inhibit T-cell function such as cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death-ligand 1 (PD-1) have demonstrated the potency of this new class of therapy, highlighted by long-term complete responses for metastatic cancers once thought incurable. However, only a subset of patients responds to checkpoint blockade because of a multitude of factors, including an immunosuppressive tumor microenvironment and the mutational burden of the cancer. Novel antibodies, as well as ligand-immunoglobulin fusion proteins that target costimulatory immune receptors, are being developed and tested in clinical trials to further enhance the anti-tumor immune response. Many of these costimulatory receptors are in the tumor necrosis factor receptor superfamily (TNFRSF) and are expressed on multiple immune cell types, including inhibitory cells. While TNFRSFs signal through common pathways, the outcome of targeting different receptors depends on the functional status of the cell types expressing the relevant receptors. In this review, we discuss the current state of targeted costimulatory immunotherapy.
- Subjects :
- Animals
Antigen-Presenting Cells immunology
CTLA-4 Antigen antagonists & inhibitors
CTLA-4 Antigen immunology
Clinical Trials as Topic
Humans
Lymphocyte Activation
Neoplasms immunology
Programmed Cell Death 1 Receptor antagonists & inhibitors
Programmed Cell Death 1 Receptor immunology
Receptors, Tumor Necrosis Factor agonists
Receptors, Tumor Necrosis Factor immunology
Antibodies, Monoclonal therapeutic use
Costimulatory and Inhibitory T-Cell Receptors immunology
Immunotherapy methods
Neoplasms drug therapy
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1179-190X
- Volume :
- 32
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 29637478
- Full Text :
- https://doi.org/10.1007/s40259-018-0277-2