| Title: |
CAR‐T cells derived from multiple myeloma patients at diagnosis have improved cytotoxic functions compared to those produced at relapse or following daratumumab treatment |
| Authors: |
Audrey Abecassis; Nathalie Roders; Maxime Fayon; Caroline Choisy; Elisabeth Nelson; Stephanie Harel; Bruno Royer; Camille Villesuzanne; Alexis Talbot; David Garrick; Michele Goodhardt; Jean‐Paul Fermand; Mike Burbridge; Bertrand Arnulf; Jean‐Christophe Bories |
| Source: |
eJHaem, Vol 3, Iss 3, Pp 970-974 (2022) |
| Publisher Information: |
Wiley |
| Publication Year: |
2022 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
CAR‐T cells; daratumumab; multiple myeloma; peripheral tcells; relapse; Diseases of the blood and blood-forming organs; RC633-647.5 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1002/jha2.479; https://doaj.org/toc/2688-6146; https://doaj.org/article/338bcbe39cad4692acdfb83db0d67b2b |
| DOI: |
10.1002/jha2.479 |
| Availability: |
https://doi.org/10.1002/jha2.479; https://doaj.org/article/338bcbe39cad4692acdfb83db0d67b2b |
| Accession Number: |
edsbas.BC3A6EB9 |
| Database: |
BASE |