TY - JOUR T1 - Combination immunotherapy: a road map JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1186/s40425-017-0218-5 VL - 5 IS - 1 SP - 16 AU - Patrick A. Ott AU - F. Stephen Hodi AU - Howard L. Kaufman AU - Jon M. Wigginton AU - Jedd D. Wolchok Y1 - 2017/12/01 UR - http://jitc.bmj.com/content/5/1/16.abstract N2 - Cancer immunotherapy and in particular monoclonal antibodies blocking the inhibitory programed cell death 1 pathway (PD-1/PD-L1) have made a significant impact on the treatment of cancer patients in recent years. However, despite the remarkable clinical efficacy of these agents in a number of malignancies, it has become clear that they are not sufficiently active for many patients. Initial evidence, for example with combined inhibition of PD-1 and CTLA-4 in melanoma and non-small cell lung cancer (NSCLC), has highlighted the potential to further enhance the clinical benefits of monotherapies by combining agents with synergistic mechanisms of action. In order to address the current progress and consider challenges associated with these novel approaches, the Society for Immunotherapy of Cancer (SITC) convened a Combination Immunotherapy Task Force. This Task Force was charged with identifying and prioritizing the most promising prospects for combinatorial approaches as well as addressing the challenges associated with developing these strategies. As a result of the extensive clinical benefit and tolerable side effects demonstrated with agents inhibiting the PD-1 pathway, an overview of current evidence to support its promising potential for use as a backbone in combination strategies is presented. In addition, key issues in the development of these strategies including preclinical modeling, patient safety and toxicity considerations, clinical trial design, and endpoints are also discussed. Overall, the goal of this manuscript is to provide a summary of the current status and potential challenges associated with the development and clinical implementation of these strategies.Abbreviations:4-HT4-hydroxytamoxifenAEAdverse eventsCARChimeric-antigen receptorCRSCytokine release syndromeCTLA-4Cytotoxic T lymphocyte associated protein 4DCDendritic cellDLTDose-limiting toxicityDMBA7,12-dimethylbenz[a]anthraceneDRRDurable response rateDTDiphtheria toxinFOXN1Forkhead box protein N1GEMMGenetically engineered mouse modelGITRGlucocorticoid-induced tumor necrosis factor receptor-related proteinGVHDGraft-versus-host diseaseIDOIndoleamine 2,3-dioxgenaseILInterleukinirAEImmune-related adverse eventIRBInstitutional review boardirRCImmune-related response criteriaMADMaximum administered doseMBEDMaximum biologically-effective doseMCAMethylcholanthreneMDSCMyeloid derived suppressor cellsMSIMicrosatellite instabilityMTMetallothionein-IMTDMaximum tolerated dosemWHOModified World Health OrganizationNKNatural killer cellNKTNatural killer T cellNSCLCNon-small cell lung cancerORRObjective response rateOSOverall survivalPD-1Programed cell death 1PD-L1Programed cell death ligand 1PFSProgression-free survivalPyMTPolyoma middle T antigenRAG-1Recombination activation geneRECISTResponse evaluation criteria in solid tumorsSCIDSevere combined immunodeficienciesSITCSociety for Immunotherapy of CancerSV40Simian virus 40TPA12-O-tetradecanoylphorbol-13-acetateTregRegulatory T cellT-VECTalimogene laherparepvec ER -