Cytotoxicity and exhaustion markers of chimeric antigen receptor T cells targeting BCMA in multiple myeloma cell lines between patients and healthy donors.

BCMA CAR cytotoxicity exhaustion multiple myeloma

Journal

European journal of haematology
ISSN: 1600-0609
Titre abrégé: Eur J Haematol
Pays: England
ID NLM: 8703985

Informations de publication

Date de publication:
24 May 2023
Historique:
revised: 07 05 2023
received: 09 04 2023
accepted: 08 05 2023
medline: 24 5 2023
pubmed: 24 5 2023
entrez: 24 5 2023
Statut: aheadofprint

Résumé

Multiple myeloma (MM) accounts for 10% of hematologic malignancies. However, most of the patients suffered from relapsed/refractory disease. We would like to expand CAR T cell therapy to treat MM using our current platform. BCMA CAR T lymphocytes were generated for volunteers or MM patients. The transduction efficiency was detected by the ddPCR technique. Immunophenotyping and exhaustion markers were monitored by flow cytometry. The efficacy of BCMA CAR T cells was tested using coculturing with BCMA CAR or mock, and the positive and negative targets, K562/hBCMA-ECTM and K562, respectively. BCMA CAR T cells were generated from consented volunteers or MM patients and could be detected CAR BCMA expression at a mean of 4.07 ± 1.95 or 4.65 ± 1.21 copies/cell, respectively. Those modified T cells were primarily effector memory T cells. Our BCMA CAR T cells could explicitly eradicate the K562/hBCMA-ECTM cell line while the K562 cell line survived. Interestingly, the BCMA CAR, mock T cells, and peripheral blood mononuclear cells from MM patients expressed similar levels of the exhaustion makers, TIM-3, LAG-3, and PD1. Our BCMA CAR T cells, mainly effector/effector memory, could eliminate BCMA-expressing cells in vitro and had similar levels of exhaustion markers among different populations.

Identifiants

pubmed: 37222081
doi: 10.1111/ejh.14007
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Fundamental Fund from Thailand Science Research and Innovation (FRB650007/0185) to Usanarat Anurathapan.
Organisme : Specific League Funds from Mahidol University

Informations de copyright

© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.

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Auteurs

Somsak Prasongtanakij (S)

Research, Academics and Innovation Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Sarinthip Preedagasamzin (S)

Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Bunyada Jittorntrum (B)

Research, Academics and Innovation Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Usanarat Anurathapan (U)

Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Teeraya Puavilai (T)

Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Pimjai Niparuck (P)

Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Pichika Chantrathammachart (P)

Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Thanakrit Piyajaroenkij (T)

Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Kitipong Uaesoontrachoon (K)

Genepeutic Bio, Co. Ltd., Bangkok, Thailand.

Ryosuke Uchibori (R)

Division of Immuno-Gene & Cell Therapy, Jichi Medical University, Tochigi-ken, Japan.

Keiya Ozawa (K)

Division of Immuno-Gene & Cell Therapy, Jichi Medical University, Tochigi-ken, Japan.

Ken Ohmine (K)

Division of Immuno-Gene & Cell Therapy, Jichi Medical University, Tochigi-ken, Japan.
Department of Medicine, School of Medicine, Jichi Medical University, Tochigi-ken, Japan.

Suradej Hongeng (S)

Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Classifications MeSH