CAR‐T cells derived from multiple myeloma patients at diagnosis have improved cytotoxic functions compared to those produced at relapse or following daratumumab treatment

Chimeric antigen receptor T cells (CAR‐T) have provided promising results in multiple myeloma (MM). However, many patients still relapse, pointing toward the need of improving this therapy. Here, we analyzed peripheral blood T cells from MM patients at different stages of the disease and investigate...

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Bibliographic Details
Published inEJHaem Vol. 3; no. 3; pp. 970 - 974
Main Authors Abecassis, Audrey, Roders, Nathalie, Fayon, Maxime, Choisy, Caroline, Nelson, Elisabeth, Harel, Stephanie, Royer, Bruno, Villesuzanne, Camille, Talbot, Alexis, Garrick, David, Goodhardt, Michele, Fermand, Jean‐Paul, Burbridge, Mike, Arnulf, Bertrand, Bories, Jean‐Christophe
Format Journal Article
LanguageEnglish
Published United States John Wiley & Sons, Inc 01.08.2022
John Wiley and Sons Inc
Wiley
Subjects
Antigens
CAR‐T cells
Chimeric antigen receptors
Cytotoxicity
daratumumab
Diagnosis
Immunological memory
Lymphocytes
Lymphocytes T
Memory cells
Multiple myeloma
Patients
Peripheral blood
peripheral tcells
Phenotypes
Ratios
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Short Report
Short Reports
peripheral tcells
multiple myeloma
CAR‐T cells
daratumumab
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Summary:Chimeric antigen receptor T cells (CAR‐T) have provided promising results in multiple myeloma (MM). However, many patients still relapse, pointing toward the need of improving this therapy. Here, we analyzed peripheral blood T cells from MM patients at different stages of the disease and investigated their phenotype and capacity to generate functional CAR‐T directed against CS1 or B Cell Maturation antigen. We found a decrease in naive T cells and elevated frequencies of exhaustion markers in T cells from treated MM patients. Interestingly, individuals treated with daratumumab display elevated ratios of central memory T cells. CAR‐T derived from patients at relapse show reduced in vitro expansion and cytotoxic capacities in response to MM cells compared to those produced at diagnosis. Of note, CAR‐T from daratumumab treated patients display intermediate defects. Reduced anti‐myeloma activity of CAR T cells from treated patients was also observed in a mouse model. Our findings suggest that T cell defects in MM patients, specifically during relapse, have a major impact on their capacity to generate efficient therapeutic CAR‐T. Selecting naive or central memory T cell subsets to generate therapeutic T cells could improve the CAR‐T therapy for MM.
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ISSN:2688-6146
2688-6146
DOI:10.1002/jha2.479