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J Immunother Cancer. 2016 Mar 15;4:15. doi: 10.1186/s40425-016-0118-0. eCollection 2016.

Immunodynamics: a cancer immunotherapy trials network review of immune monitoring in immuno-oncology clinical trials.

Author information

1
Division of Oncology, Stanford Cancer Institute, Stanford University Medical Center, 269 Campus Drive, CCSR 1105, Stanford, CA 94305-5151 USA.
2
Division of Dermatology, Department of Medicine, University of California Los Angeles, Los Angeles, CA USA.
3
Division of Hematology/Oncology, Ohio State University, Columbus, OH USA.
4
Medicine, Hematology and Medical Oncology, Mount Sinai Hospital, New York, NY USA.
5
Medicine, Hematology and Medical Oncology, Mount Sinai Hospital, Ruttenberg Treatment Center, New York, NY USA.
6
Department of Radiation Oncology, New York Weill Cornell Medical Center, New York, NY USA.
7
SOM-Molecular Microbiology & Immunology Department, Laboratory of Molecular and Tumor Immunology, OHSU Cancer Institute, Portland, OR USA.
8
INSERM, Integrative Cancer Immunology Team, Cordeliers Research Center, Paris, France.
9
Perelman School of Medicine, University of Pennsylvania, Pathology and Laboratory Medicine, Philadelphia, PA USA.
10
Cancer Immunobiology, Eli Lilly & Company, New York, NY USA.
11
Translational Medicine, Adaptive Biotechnologies Corp, Seattle, WA USA.
12
Immune Monitoring, Epiontis GmbH, Berlin, Germany.
13
Faculty of Medicine, University of Paris Descartes, Paris, France.
14
Department of Microbiology and Immunology, University of California, San Francisco, CA USA.
15
Division of Oncology, Stanford School of Medicine, Stanford, CA USA.
16
Duke University School of Medicine, Durham, NC USA.
17
Human Immune Monitoring Center Shared Resource, Stanford Cancer Institute, Stanford, CA USA.
18
Léon Bérard Cancer Center, Lyon, France.
19
Product Development and Correlative Sciences, Smilow Center for Translational Research, Philadelphia, PA USA.
20
Division of Hematology, Experimental Therapeutics, University of Minnesota, Oncology and Transplantation, Minneapolis, MN USA.
21
Centro de Investigacion Medica Aplicada, Universidad de Navarra, Avda. Pamplona, Spain.
22
Center for Immunotherapy, Roswell Park Cancer Institute, Buffalo, NY USA.
23
Baylor Institute for Immunology Research, Dallas, TX USA.
24
Cancer Vaccine Development Program, Brooke Army Medical Center, Houston, TX USA.
25
Tumor Immunology Program Area, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA USA.
26
Adaptive Biotechnologies, Seattle, WA USA.
27
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA USA.
28
Atreca, Inc, Redwood City, CA USA.
29
Cellular & Molecular Pathology Graduate Program, University of Wisconsin-Madison, Madison, WI USA.
30
Centre d'Immunologie de Marseille-Luminy, Marseille, France.
31
Moffitt Cancer Center, Tampa, FL USA.
32
Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY USA.
33
Institut National de la Santé et Recherche Médicale, Institut GrustaveRoussy, Villejuif, France.
34
Tumor Vaccine Group, University of Washington, Seattle, WA USA.
35
Fred Hutchinson Cancer Research Center, 1100 Eastlake Ave N., E3-300, PO Box 19024, Seattle, WA 98109-1023 USA.
#
Contributed equally

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.

KEYWORDS:

Biomarker; Clinical trial; Immunotherapy

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