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Inhibitors of B7-CD28 costimulation in urologic malignancies.
- Source :
-
Immunotherapy [Immunotherapy] 2009 Jan; Vol. 1 (1), pp. 129-39. - Publication Year :
- 2009
-
Abstract
- T-cell costimulatory molecules deliver positive or negative signals to govern the ultimate fate of immune responses. These ligands and receptors that negatively costimulate T cells (including cytotoxic T-lymphocyte antigen [CTLA]-4, B7-H1, programmed death [PD]-1, B7-H3 and B7x) have received significant interest recently owing to their proposed ability to form a molecular shield for tumor cells. CTLA-4 represents the most extensively studied receptor in the costimulatory pathway and functions as a potent inhibitor of T-cell-mediated immunity. Clinical trials with anti-CTLA-4 are ongoing, although numerous objective responses have been observed in heavily pretreated patients, albeit with autoimmune side effects. In renal cell carcinoma, B7-H1, PD-1 and B7x have been observed to be expressed on tumor cells or infiltrating lymphocytes and are individually associated with adverse pathologic features and poor clinical outcome. In prostate cancer, B7-H3 and B7x immunostaining intensity correlate with disease spread, clinical cancer recurrence and cancer-specific death. External validation and prospective studies are now needed to confirm these findings, while further development of humanized monoclonal antibodies, similar to the experience with anti-CTLA-4, are underway. Herein, we review the B7-CD28 family as it applies to urologic malignancies.
- Subjects :
- Antibodies, Blocking pharmacology
Antibodies, Blocking therapeutic use
Antigens, CD immunology
Antigens, CD metabolism
Apoptosis Regulatory Proteins immunology
Apoptosis Regulatory Proteins metabolism
B7-1 Antigen genetics
B7-1 Antigen immunology
Biomarkers, Tumor genetics
Biomarkers, Tumor immunology
CD28 Antigens immunology
CTLA-4 Antigen
Carcinoma pathology
Carcinoma therapy
Clinical Trials as Topic
Disease Progression
Gene Expression Regulation, Neoplastic drug effects
Gene Expression Regulation, Neoplastic immunology
Immunity, Cellular drug effects
Kidney Neoplasms pathology
Kidney Neoplasms therapy
Programmed Cell Death 1 Receptor
Signal Transduction drug effects
Signal Transduction immunology
T-Lymphocytes, Cytotoxic drug effects
T-Lymphocytes, Cytotoxic immunology
T-Lymphocytes, Cytotoxic pathology
B7-1 Antigen metabolism
Biomarkers, Tumor metabolism
CD28 Antigens metabolism
Carcinoma immunology
Immunotherapy
Kidney Neoplasms immunology
T-Lymphocytes, Cytotoxic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1750-7448
- Volume :
- 1
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Immunotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 20445772
- Full Text :
- https://doi.org/10.2217/1750743X.1.1.129