Inhibitors of B7-CD28 costimulation in urologic malignancies Journal Article
| Authors: | Thompson, R. H.; Kwon, E. D.; Allison, J. P. |
| Article Title: | Inhibitors of B7-CD28 costimulation in urologic malignancies |
| 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. © 2009 Future Medicine Ltd. |
| Keywords: | unclassified drug; clinical trial; review; cancer recurrence; cancer growth; nonhuman; antigen expression; cytotoxic t lymphocyte antigen 4 antibody; ipilimumab; ticilimumab; cancer immunotherapy; protein; renal cell carcinoma; kidney carcinoma; cancer mortality; prostate cancer; regulatory t lymphocyte; lymphocyte activation; cellular immunity; cytotoxic t lymphocyte; urinary tract cancer; tumor immunity; kidney cancer; cytotoxic t lymphocyte antigen 4; granulocyte macrophage colony stimulating factor vaccine; autoimmune disease; cd28 antigen; b7 antigen; prostatic neoplasm; urinary bladder neoplasm; b7 h3 antigen; b7x antigen; human monoclonal antibody; programmed death 1 ligand 1; programmed death 1 receptor |
| Journal Title: | Immunotherapy |
| Volume: | 1 |
| Issue: | 1 |
| ISSN: | 1750-743X |
| Publisher: | Future Medicine |
| Date Published: | 2009-01-01 |
| Start Page: | 129 |
| End Page: | 139 |
| Language: | English |
| DOI: | 10.2217/1750743x.1.1.129 |
| PROVIDER: | scopus |
| PMCID: | PMC2864044 |
| PUBMED: | 20445772 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 30 November 2010" - "Source: Scopus" |
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