Integrating costimulatory agonists to optimize immune-based cancer therapies.
While immunotherapy for cancer has become increasingly popular, clinical benefits for such approaches remain limited. This is likely due to tumor-associated immune suppression, particularly in the advanced-disease setting. Thus, a major goal of novel immunotherapeutic design has become the coordinate reversal of existing immune dysfunction and promotion of specific tumoricidal T-cell function. Costimulatory members of the TNF-receptor family are important regulators of T-cell-mediated immunity. Notably, agonist ligation of these receptors restores potent antitumor immunity in the tumor-bearing host. Current Phase I/II evaluation of TNF-receptor agonists as single-modality therapies will illuminate their safety, mechanism(s) of action, and best use in prospective combinational immunotherapy approaches capable of yielding superior benefits to cancer patients.
Pardee
Angela D
AD
University of Pittsburgh School of Medicine, PA, Pittsburgh, USA.
Wesa
Amy K
AK
Storkus
Walter J
WJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007114:Immunization; D007167:Immunotherapy; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000819:agonists; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019139:Tumor Escape / Q000187:drug effects
D000970:Antineoplastic Agents; D018124:Receptors, Tumor Necrosis Factor