Propelling Immunotherapy Combinations Into the Clinic.

摘要: Immune checkpoint inhibitors produce durable long-term survival in some patients with advanced melanoma and lung cancer. Better immune targets combination strategies can harness the system by supporting three elements of a successful T-cell antitumor response: (A) generation sufficient numbers T cells within lymphoid compartment; (B) effective trafficking extravasation out compartment, through bloodstream, into tumor microenvironment; (C) effector function microenvironment that is characterized ability to bypass checkpoints, soluble metabolic inhibitory factors, cells. Strategies hold promise include dual blockade, as well blockade costimulatory receptor agonists, enhancers innate immunity, inhibition indoleamine 2,3-dioxygenase, adoptive transfer/T-cell engineering, therapeutic vaccines, small-molecule inhibitors, radiation therapy. Novel, rational clinical trial designs seek combine targeted agents one or more goal producing deep responses, which thus far have been observed only minority patients.