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CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide

Author

Listed:
  • Sabarinath V. Radhakrishnan

    (University of Utah)

  • Tim Luetkens

    (University of Utah)

  • Sandra D. Scherer

    (University of Utah)

  • Patricia Davis

    (University of Utah and ARUP Laboratories)

  • Erica R. Vander Mause

    (University of Utah)

  • Michael L. Olson

    (University of Utah)

  • Sara Yousef

    (University of Utah)

  • Jens Panse

    (University Hospital RWTH Aachen)

  • Yasmina Abdiche

    (Carterra Inc.)

  • K. David Li

    (University of Utah and ARUP Laboratories)

  • Rodney R. Miles

    (University of Utah and ARUP Laboratories)

  • William Matsui

    (The University of Texas at Austin)

  • Alana L. Welm

    (University of Utah)

  • Djordje Atanackovic

    (University of Utah)

Abstract

Multiple myeloma (MM) is a plasma cell malignancy and most patients eventually succumb to the disease. Chimeric antigen receptor (CAR) T cells targeting B-Cell Maturation Antigen (BCMA) on MM cells have shown high-response rates, but limited durability. CD229/LY9 is a cell surface receptor present on B and T lymphocytes that is universally and strongly expressed on MM plasma cells. Here, we develop CD229 CAR T cells that are highly active in vitro and in vivo against MM plasma cells, memory B cells, and MM-propagating cells. We do not observe fratricide during CD229 CAR T cell production, as CD229 is downregulated in T cells during activation. In addition, while CD229 CAR T cells target normal CD229high T cells, they spare functional CD229neg/low T cells. These findings indicate that CD229 CAR T cells may be an effective treatment for patients with MM.

Suggested Citation

  • Sabarinath V. Radhakrishnan & Tim Luetkens & Sandra D. Scherer & Patricia Davis & Erica R. Vander Mause & Michael L. Olson & Sara Yousef & Jens Panse & Yasmina Abdiche & K. David Li & Rodney R. Miles , 2020. "CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14619-z
    DOI: 10.1038/s41467-020-14619-z
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    Cited by:

    1. Ian D. Ferguson & Bonell Patiño-Escobar & Sami T. Tuomivaara & Yu-Hsiu T. Lin & Matthew A. Nix & Kevin K. Leung & Corynn Kasap & Emilio Ramos & Wilson Nieves Vasquez & Alexis Talbot & Martina Hale & A, 2022. "The surfaceome of multiple myeloma cells suggests potential immunotherapeutic strategies and protein markers of drug resistance," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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