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

患者和健康供体之间的多发性骨髓瘤细胞系中针对 BCMA 的嵌合抗原受体 T 细胞的细胞毒性和耗竭标志物

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作者:Somsak Prasongtanakij, Sarinthip Preedagasamzin, Bunyada Jittorntrum, Usanarat Anurathapan, Teeraya Puavilai, Pimjai Niparuck, Pichika Chantrathammachart, Thanakrit Piyajaroenkij, Kitipong Uaesoontrachoon, Ryosuke Uchibori, Keiya Ozawa, Ken Ohmine, Suradej Hongeng

Conclusions

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.

Methods

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.

Results

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. Conclusions: 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.

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