Harnessing co-stimulatory TNF receptors for cancer immunotherapy: Current approaches and future opportunities
| Autor: | Randi Gombos, Nicholas S. Wilson, Jeremy D. Waight |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
T-Lymphocytes medicine.medical_treatment Immunology Context (language use) Receptors Tumor Necrosis Factor 03 medical and health sciences Antineoplastic Agents Immunological 0302 clinical medicine Immune system Cancer immunotherapy Co-stimulation Antigens CD Antigens Neoplasm Neoplasms Animals Humans Immunology and Allergy Medicine CD134 Immunity Cellular business.industry Receptors IgG CD137 General Medicine Immunotherapy 030104 developmental biology Gene Expression Regulation Receptor clustering business Neuroscience Signal Transduction 030215 immunology |
| Zdroj: | Human Antibodies. 25:87-109 |
| ISSN: | 1875-869X 1093-2607 |
| Popis: | Co-stimulatory tumor necrosis factor receptors (TNFRs) can sculpt the responsiveness of T cells recognizing tumor-associated antigens. For this reason, agonist antibodies targeting CD137, CD357, CD134 and CD27 have received considerable attention for their therapeutic utility in enhancing anti-tumor immune responses, particularly in combination with other immuno-modulatory antibodies targeting co-inhibitory pathways in T cells. The design of therapeutic antibodies that optimally engage and activate co-stimulatory TNFRs presents an important challenge of how to promote effective anti-tumor immunity while avoiding serious immune-related adverse events. Here we review our current understanding of the expression, signaling and structural features of CD137, CD357, CD134 and CD27, and how this may inform the design of pharmacologically active immuno-modulatory antibodies targeting these receptors. This includes the integration of our emerging knowledge of the role of Fcγ receptors (FcγRs) in facilitating antibody-mediated receptor clustering and forward signaling, as well as promoting immune effector cell-mediated activities. Finally, we bring our current preclinical and clinical knowledge of co-stimulatory TNFR antibodies into the context of opportunities for next generation molecules with improved pharmacologic properties. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|