TY - JOUR
T1 - Single-Cell Transcriptomic Analysis Reveals BCMA CAR-T Cell Dynamics in a Patient with Refractory Primary Plasma Cell Leukemia
AU - Li, Xue
AU - Guo, Xin
AU - Zhu, Yuqing
AU - Wei, Guoqing
AU - Zhang, Yanlei
AU - Li, Xia
AU - Xu, Huijun
AU - Cui, Jiazhen
AU - Wu, Wenjun
AU - He, Jingsong
AU - Ritchie, Matthew E.
AU - Weiskittel, Taylor M.
AU - Li, Hu
AU - Yu, Hua
AU - Ding, Lijuan
AU - Shao, Mi
AU - Luo, Qian
AU - Xu, Xiaoxiao
AU - Teng, Xinyi
AU - Chang, Alex H.
AU - Zhang, Jin
AU - Huang, He
AU - Hu, Yongxian
N1 - Publisher Copyright:
© 2020 The American Society of Gene and Cell Therapy
PY - 2021/2/3
Y1 - 2021/2/3
N2 - 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.
AB - 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.
KW - chimeric antigen receptor T cell
KW - plasma cell leukemia
KW - single-cell RNA sequencing
UR - http://www.scopus.com/inward/record.url?scp=85098196169&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85098196169&partnerID=8YFLogxK
U2 - 10.1016/j.ymthe.2020.11.028
DO - 10.1016/j.ymthe.2020.11.028
M3 - Article
C2 - 33278564
AN - SCOPUS:85098196169
SN - 1525-0016
VL - 29
SP - 645
EP - 657
JO - Molecular Therapy
JF - Molecular Therapy
IS - 2
ER -