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Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy

64 Pages Posted: 26 Feb 2019 Sneak Peek Status: Review Complete

See all articles by Felix J. Hartmann

Felix J. Hartmann

Stanford University - Department of Pathology

Joel Babdor

University of California, San Francisco (UCSF), School of Medicine, Department of Otolaryngology-Head and Neck Surgery; University of California, San Francisco (UCSF), School of Medicine, Department of Microbiology and Immunology

Pier Federico Gherardini

Parker Institute for Cancer Immunotherapy

El-Ad D. Amir

Astrolabe Diagnostics, Inc.

Kyle Jones

University of California, San Francisco (UCSF), School of Medicine, Department of Orofacial Sciences

Bita Sahaf

Stanford University, School of Medicine, Cancer Institute, Cancer Correlative Science Unit

Diana M. Marquez

University of California, San Francisco (UCSF), School of Medicine, Department of Otolaryngology-Head and Neck Surgery; University of California, San Francisco (UCSF), School of Medicine, Department of Microbiology and Immunology

Peter Krutzik

Primity Bio

Erika O’Donnell

Primity Bio

Natalia Sigal

Stanford University, School of Medicine, Department of Microbiology and Immunology

Holden T. Maecker

Stanford University, School of Medicine, Department of Microbiology and Immunology

Everett Meyer

Stanford University, School of Medicine, Blood and Marrow Transplantation, Cellular Therapy Facility

Matthew Spitzer

University of California, San Francisco (UCSF), School of Medicine, Department of Otolaryngology-Head and Neck Surgery; University of California, San Francisco (UCSF), School of Medicine, Department of Microbiology and Immunology; Parker Institute for Cancer Immunotherapy; Stanford University - Chan Zuckerberg Biohub

Sean C. Bendall

Stanford University - Department of Pathology

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Abstract

The success of immunotherapy has led to a myriad of new clinical trials. Connected to these trials are efforts to discover biomarkers providing mechanistic insight and predictivesignatures for personalization. Still, the plethora of immune monitoring technologies can face investigator bias, missing unanticipated cellular responses in limited clinical material. We here present a mass cytometry workflow for standardized, systems-level biomarker discovery in immunotherapy trials. To broadly enumerate human immune cell identity and activity, we established and extensively assessed a reference panel of 33 antibodies to cover major cell subsets, simultaneously quantifying activation and immune checkpoint molecules in a single assay. The resulting assay enumerated ³ 98% of peripheral immune cells with ³ 4 positively identifying antigens. Robustness and reproducibility were demonstrated on multiple samples types, across research centers and by orthogonal measurements. Using automated analysis, we monitored complex immune dynamics, identifying signatures in bone-marrow transplantation associated graft-versus-host disease. This validated and available workflow ensures comprehensive immunophenotypic analysis, data comparability and will accelerate biomarker discovery in immunomodulatory therapeutics.

Keywords: Immunotherapy, Cancer, Phenotyping, Monitoring, Mass Cytometry, Biomarker, CyTOF, Bone Marrow Transplantation

Suggested Citation

Hartmann, Felix J. and Babdor, Joel and Gherardini, Pier Federico and Amir, El-Ad D. and Jones, Kyle and Sahaf, Bita and Marquez, Diana M. and Krutzik, Peter and O’Donnell, Erika and Sigal, Natalia and Maecker, Holden T. and Meyer, Everett and Spitzer, Matthew and Bendall, Sean C., Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy (December 28, 2018). Available at SSRN: https://ssrn.com/abstract=3307227 or http://dx.doi.org/10.2139/ssrn.3307227
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Felix J. Hartmann

Stanford University - Department of Pathology

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

Joel Babdor

University of California, San Francisco (UCSF), School of Medicine, Department of Otolaryngology-Head and Neck Surgery

CA
United States

University of California, San Francisco (UCSF), School of Medicine, Department of Microbiology and Immunology

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Pier Federico Gherardini

Parker Institute for Cancer Immunotherapy

San Francisco, CA
United States

El-Ad D. Amir

Astrolabe Diagnostics, Inc.

Fort Lee, NJ 07024
United States

Kyle Jones

University of California, San Francisco (UCSF), School of Medicine, Department of Orofacial Sciences

San Francisco, CA
United States

Bita Sahaf

Stanford University, School of Medicine, Cancer Institute, Cancer Correlative Science Unit

Palo Alto, CA
United States

Diana M. Marquez

University of California, San Francisco (UCSF), School of Medicine, Department of Otolaryngology-Head and Neck Surgery

CA
United States

University of California, San Francisco (UCSF), School of Medicine, Department of Microbiology and Immunology

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Peter Krutzik

Primity Bio

Fremont, CA 94538
United States

Erika O’Donnell

Primity Bio

Fremont, CA 94538
United States

Natalia Sigal

Stanford University, School of Medicine, Department of Microbiology and Immunology

Stanford, CA 94305
United States

Holden T. Maecker

Stanford University, School of Medicine, Department of Microbiology and Immunology

Stanford, CA 94305
United States

Everett Meyer

Stanford University, School of Medicine, Blood and Marrow Transplantation, Cellular Therapy Facility

Palo Alto, CA
United States

Matthew Spitzer (Contact Author)

University of California, San Francisco (UCSF), School of Medicine, Department of Otolaryngology-Head and Neck Surgery ( email )

CA
United States

University of California, San Francisco (UCSF), School of Medicine, Department of Microbiology and Immunology ( email )

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Parker Institute for Cancer Immunotherapy ( email )

San Francisco, CA
United States

Stanford University - Chan Zuckerberg Biohub ( email )

499 Illinois Street
San Francisco, CA 94158
United States

Sean C. Bendall

Stanford University - Department of Pathology ( email )

291 Campus Drive
Li Ka Shing Building
Stanford, CA 94305-5101
United States

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