Single-cell transcriptomic analysis reveals BCMA CAR-T cell dynamics in a patient with refractory primary plasma cell leukemia

Li, X; Guo, X; Zhu, Y; Wei, G; Zhang, Y; Li, X; Xu, H; Cui, J; Wu, W; He, J; Ritchie, ME; Weiskittel, TM; Li, H; Yu, H; Ding, L; Shao, M; Luo, Q; Xu, X; Teng, X; Chang, AH; Zhang, J; Huang, H; Hu, Y

Author(s): Li, X; Guo, X; Zhu, Y; Wei, G; Zhang, Y; Li, X; Xu, H; Cui, J; Wu, W; He, J; Ritchie, ME; Weiskittel, TM; Li, H; Yu, H; Ding, L; Shao, M; Luo, Q; Xu, X; Teng, X; Chang, AH; Zhang, J; Huang, H; Hu, Y;
Details: Publication Year 2021-02-03,Volume 29,Issue #2,Page 645-657
Journal Title: Molecular Therapy
Abstract: Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the clinical treatment of hematological malignancies due to the prominent anti-tumor effects. B cell maturation antigen (BCMA) CAR-T cells have demonstrated promising effects in patients with relapsed/refractory multiple myeloma. However, the dynamics of CAR-T cell proliferation and cytotoxicity in clinical patients remains unexplored. Here, we longitudinally profiled the transcriptomes of 55,488 T cells including CAR-T products, CAR-T cells, and endogenous T cells at the peak and remission phases in a plasma cell leukemia (PCL) patient treated with BCMA CAR-T cells by single-cell transcriptomic analysis. Our results showed distinct CAR-T and endogenous T cell subsets indicating stage-specific expression in proliferation, cytotoxicity, and intercellular signaling pathways. Furthermore, we found that CAR-T cells at peak phase gradually convert to a highly cytotoxic state from a highly proliferative state along a development trajectory. Moreover, re-analysis of a single cell study from CD8(+) CD19 CAR-T confirmed our findings. These commonalities suggest conserved mechanisms for CAR-T treatment across hematological malignancies. Taken together, our current study provides insight into CAR-T cell dynamics during CAR-T therapy and proves that both BCMA CAR-T and CD19 CAR-T have similar transcriptional characteristics, especially at the CAR-T peak phase.
Publisher: Elsevier
Keywords: chimeric antigen receptor T cell; plasma cell leukemia; single-cell RNA sequencing
Research Division(s): Epigenetics And Development
PubMed ID: 33278564
Publisher's Version: https://doi.org/10.1016/j.ymthe.2020.11.028
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2021-03-02 02:15:36

Last Modified: 2021-03-02 02:18:42