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Sensitive, Non‐Destructive Detection and Analysis of Neoantigen‐Specific T Cell Populations from Tumors and Blood

47 Pages Posted: 12 Apr 2018 Sneak Peek Status: Review Complete

See all articles by Songming Peng

Songming Peng

California Institute of Technology - Division of Chemistry and Chemical Engineering

Jesse M. Zaretsky

University of California, Los Angeles (UCLA) - Department of Medicine; University of California, Los Angeles (UCLA) - Jonsson Comprehensive Cancer Center

Michael T. Bethune

California Institute of Technology - Division of Biology and Biological Engineering

Alice Hsu

California Institute of Technology - Division of Biology and Biological Engineering

Elizabeth Holman

California Institute of Technology - Division of Chemistry and Chemical Engineering

Xiaozhe Ding

California Institute of Technology - Division of Chemistry and Chemical Engineering; California Institute of Technology - Division of Biology and Biological Engineering

Katherine Guo

California Institute of Technology - Division of Biology and Biological Engineering

Jungwoo Kim

California Institute of Technology - Division of Chemistry and Chemical Engineering

Alexander M. Xu

California Institute of Technology - Division of Chemistry and Chemical Engineering

John E. Heath

California Institute of Technology - Division of Chemistry and Chemical Engineering

Won Jun Noh

California Institute of Technology - Division of Biology and Biological Engineering

Jing Zhou

California Institute of Technology - Division of Chemistry and Chemical Engineering

Yapeng Su

California Institute of Technology - Division of Chemistry and Chemical Engineering

Jami McLaughlin

University of California, Los Angeles (UCLA) - Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research

Donghui Cheng

University of California, Los Angeles (UCLA) - Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research

Owen N. Witte

University of California, Los Angeles (UCLA) - Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research; University of California, Los Angeles (UCLA) - Department of Microbiology, Immunology and Molecular Genetics; University of California, Los Angeles (UCLA) - Howard Hughes Medical Institute (HHMI)

David Baltimore

California Institute of Technology - Division of Biology and Biological Engineering

Antoni Ribas

University of California, Los Angeles (UCLA) - Department of Medicine; University of California, Los Angeles (UCLA) - Jonsson Comprehensive Cancer Center

James R. Heath

California Institute of Technology - Division of Chemistry and Chemical Engineering

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Abstract

Tumor neoantigens are fragments of mutated proteins that contain the mutation, and can be presented by major histocompatibility complex molecules on tumor cells, where they are surveyed by T cells. The rapid and sensitive identification of neoantigen‐specific T cell populations from tumor tissues or blood has proven challenging. A microchip platform for the non‐destructive identification of neoantigen‐specific CD8 T cells is described. The method utilizes a library of neoantigen/MHC tetramers linked to a magnetic nanoparticle via a DNA barcode. The neoantigen‐specificity of the T cells is determined by decoding the barcode through sequential fluorescent microscopy reads. The captured T cells may be further characterized for function, or via matching the neoantigen‐specificity with the T cell receptor gene. Tumor infiltrating lymphocytes and non‐expanded peripheral blood mononuclear cells collected from melanoma patients at various time points across an anti‐PD1 therapy regimen are shown to contain overlapping neoantigen‐specific T cell populations.

Suggested Citation

Peng, Songming and Zaretsky, Jesse M. and Bethune, Michael T. and Hsu, Alice and Holman, Elizabeth and Ding, Xiaozhe and Guo, Katherine and Kim, Jungwoo and Xu, Alexander M. and Heath, John E. and Noh, Won Jun and Zhou, Jing and Su, Yapeng and McLaughlin, Jami and Cheng, Donghui and Witte, Owen N. and Baltimore, David and Ribas, Antoni and Heath, James R., Sensitive, Non‐Destructive Detection and Analysis of Neoantigen‐Specific T Cell Populations from Tumors and Blood (2018). Available at SSRN: https://ssrn.com/abstract=3155791 or http://dx.doi.org/10.2139/ssrn.3155791
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Songming Peng

California Institute of Technology - Division of Chemistry and Chemical Engineering

1200 East California Boulevard
Pasadena, CA 91125
United States

Jesse M. Zaretsky

University of California, Los Angeles (UCLA) - Department of Medicine

Los Angeles, CA
United States

University of California, Los Angeles (UCLA) - Jonsson Comprehensive Cancer Center

10833 Le Conte Avenue
Los Angeles, CA 90095-6939
United States

Michael T. Bethune

California Institute of Technology - Division of Biology and Biological Engineering

Pasadena, CA 91125
United States

Alice Hsu

California Institute of Technology - Division of Biology and Biological Engineering

Pasadena, CA 91125
United States

Elizabeth Holman

California Institute of Technology - Division of Chemistry and Chemical Engineering

1200 East California Boulevard
Pasadena, CA 91125
United States

Xiaozhe Ding

California Institute of Technology - Division of Chemistry and Chemical Engineering

1200 East California Boulevard
Pasadena, CA 91125
United States

California Institute of Technology - Division of Biology and Biological Engineering

Pasadena, CA 91125
United States

Katherine Guo

California Institute of Technology - Division of Biology and Biological Engineering

Pasadena, CA 91125
United States

Jungwoo Kim

California Institute of Technology - Division of Chemistry and Chemical Engineering

1200 East California Boulevard
Pasadena, CA 91125
United States

Alexander M. Xu

California Institute of Technology - Division of Chemistry and Chemical Engineering

1200 East California Boulevard
Pasadena, CA 91125
United States

John E. Heath

California Institute of Technology - Division of Chemistry and Chemical Engineering

1200 East California Boulevard
Pasadena, CA 91125
United States

Won Jun Noh

California Institute of Technology - Division of Biology and Biological Engineering

Pasadena, CA 91125
United States

Jing Zhou

California Institute of Technology - Division of Chemistry and Chemical Engineering

1200 East California Boulevard
Pasadena, CA 91125
United States

Yapeng Su

California Institute of Technology - Division of Chemistry and Chemical Engineering

1200 East California Boulevard
Pasadena, CA 91125
United States

Jami McLaughlin

University of California, Los Angeles (UCLA) - Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research

615 Charles E Young Dr. S.
Los Angeles, CA 90095
United States

Donghui Cheng

University of California, Los Angeles (UCLA) - Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research

615 Charles E Young Dr. S.
Los Angeles, CA 90095
United States

Owen N. Witte

University of California, Los Angeles (UCLA) - Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research

615 Charles E Young Dr. S.
Los Angeles, CA 90095
United States

University of California, Los Angeles (UCLA) - Department of Microbiology, Immunology and Molecular Genetics

1602 Molecular Sciences Building
609 Charles E. Young Drive, East
Los Angeles, CA 90095
United States

University of California, Los Angeles (UCLA) - Howard Hughes Medical Institute (HHMI)

Los Angeles, CA 90095-6939
United States

David Baltimore

California Institute of Technology - Division of Biology and Biological Engineering

Pasadena, CA 91125
United States

Antoni Ribas

University of California, Los Angeles (UCLA) - Department of Medicine

Los Angeles, CA
United States

University of California, Los Angeles (UCLA) - Jonsson Comprehensive Cancer Center

10833 Le Conte Avenue
Los Angeles, CA 90095-6939
United States

James R. Heath (Contact Author)

California Institute of Technology - Division of Chemistry and Chemical Engineering ( email )

1200 East California Boulevard
Pasadena, CA 91125
United States

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