Immunodynamics: a cancer immunotherapy trials network review of immune monitoring in immuno-oncology clinical trials
Year: 2016
Type: article
Abstract: The efficacy of PD-1/PD-L1 targeted therapies in addition to anti-CTLA-4 solidifies immunotherapy as a modality to add to the anticancer arsenal. Despite raising the bar of clinical efficacy, immunologically targeted agents raise new challenges to conventional drug development paradigms by highlighting the limited relevance of assessing standard pharmacokinetics (PK) and pharmacodynamics (PD). Specifically, systemic and intratumoral immune effects have not consistently correlated with standard relationships between systemic dose, toxicity, and efficacy for cytotoxic therapies. Hence, PK and PD paradigms remain inadequate to guide the selection of doses and schedules, both starting and recommended Phase 2 for immunotherapies. The promise of harnessing the immune response against cancer must also be considered in light of unique and potentially serious toxicities. Refining immune endpoints to better inform clinical trial design represents a high priority challenge. The Cancer Immunotherapy Trials Network investigators review the immunodynamic effects of specific classes of immunotherapeutic agents to focus immune assessment modalities and sites, both systemic and importantly intratumoral, which are critical to the success of the rapidly growing field of immuno-oncology.
Authors: on behalf of the Cancer Immunotherapy Trials Network (CITN), Holbrook E. Kohrt, Paul C. Tumeh, Don Benson, Nina Bhardwaj, Joshua Brody, Silvia Formenti, Bernard A. Fox, Jerome Galon, Carl H. June, Michael Kalos, Ilan Kirsch, Thomas Kleen, Guido Kroemer, Lewis Lanier, Ron Levy, H. Kim Lyerly, Holden Maecker, Aurelien Marabelle, Jos Melenhorst, Jeffrey Miller, Ignacio Melero, Kunle Odunsi, Karolina Palucka, George Peoples, Antoni Ribas, Harlan Robins, William Robinson, Tito Serafini, Paul Sondel, Eric Vivier, Jeff Weber, Jedd Wolchok, Laurence Zitvogel, Mary L. Disis, Martin A. Cheever
Institutions: Stanford Medicine, Stanford Cancer Institute, University of California, Los Angeles, The Ohio State University, Mount Sinai Hospital, Mount Sinai Hospital, Mount Sinai Hospital, Mount Sinai Hospital, Weill Cornell Medical Center, Oregon Health & Science University, Weill Cornell Medicine, Inserm, Centre de Recherche des Cordeliers, University of Pennsylvania, Eli Lilly (United States), Adaptive Biotechnologies (United States), Université Paris Descartes, University of California, San Francisco, Stanford University, Duke University, Centre Léon Bérard, University of Minnesota, Centro de Investigación Médica Aplicada, Universidad de Navarra, Roswell Park Comprehensive Cancer Center, Baylor University, Brooke Army Medical Center, UCLA Jonsson Comprehensive Cancer Center, University of Wisconsin–Madison, Centre d’Immunologie de Marseille-Luminy, Moffitt Cancer Center, Memorial Sloan Kettering Cancer Center, Institut Gustave Roussy, University of Washington, Fred Hutch Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W2297174255