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Distinct cellular dynamics associated with response to CAR-T therapy for refractory B cell lymphoma by Nicholas J. Haradhvala; Mark B. Leick; Katie Maurer; Satyen H. Gohil; Rebecca C. Larson; Ning Yao; Kathleen M. E. Gallagher; Katelin Katsis; Matthew J. Frigault; Jackson Southard; Shuqiang Li; Michael C. Kann; Harrison Silva; Max Jan; Kahn Rhrissorrakrai; Filippo Utro; Chaya Levovitz; Raquel A. Jacobs; Kara Slowik; Brian P. Danysh; Kenneth J. Livak; Laxmi Parida; Judith Ferry; Caron Jacobson; Catherine J. Wu; Gad Getz; Marcela V. Maus is a Medicine article available to read on EtoBox.

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Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of hematologic malignancies. Approximately half of patients with refractory large B cell lymphomas achieve durable responses from CD19-targeting CAR-T treatment; however, failure mechanisms are identified in only a fraction of cases. To gain new insights into the basis of clinical response, we performed single-cell transcriptome sequencing of 105 pretreatment and post-treatment peripheral blood mononuclear cell samples, and infusion products collected from 32 individuals with large B cell lymphoma treated with either of two CD19 CAR-T products: axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel). Expansion of proliferative memory-like CD8 clones was a hallmark of tisa-cel response, whereas axi-cel responders displayed more heterogeneous populations. Elevations in CAR-T regulatory cells among nonresponders to axi-cel were detected, and these populations were capable of suppressing conventional CAR-T cell expansion and driving late relapses in an in vivo model. Our analyses reveal the temporal dynamics of effective responses to CAR-T therapy, the distinct molecular phenotypes of CAR-T cells w

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Author

Nicholas J. Haradhvala; Mark B. Leick; Katie Maurer; Satyen H. Gohil; Rebecca C. Larson; Ning Yao; Kathleen M. E. Gallagher; Katelin Katsis; Matthew J. Frigault; Jackson Southard; Shuqiang Li; Michael C. Kann; Harrison Silva; Max Jan; Kahn Rhrissorrakrai; Filippo Utro; Chaya Levovitz; Raquel A. Jacobs; Kara Slowik; Brian P. Danysh; Kenneth J. Livak; Laxmi Parida; Judith Ferry; Caron Jacobson; Catherine J. Wu; Gad Getz; Marcela V. Maus

Publisher

Springer Science and Business Media LLC

Published

2022

Language

EN

Field

Medicine (Health Sciences)