Details

Autor(en) / Beteiligte

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

Titel

Distinct cellular dynamics associated with response to CAR-T therapy for refractory B cell lymphoma

Ist Teil von

• Nature medicine, 2022-09, Vol.28 (9), p.1848-1859

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 with differing designs, and the capacity for even small increases in CAR-T regulatory cells to drive relapse.