期刊
CLINICAL CANCER RESEARCH
卷 28, 期 15, 页码 3378-3386出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-22-0164
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类别
资金
- Alleanza Contro il Cancro
- Associazione Italiana contro le Leucemie-Linfomi e mieloma
- Associazione Italiana Ricerca sul Cancro
- Italian Ministry of Health (Ricerca Finalizzata)
This study found that the in vivo expansion of CAR T cells is associated with therapeutic efficacy. Additionally, the content and characteristics of CAR T bag cells have a significant impact on in vivo expansion, treatment response, and survival.
Purpose: In clinical trials, the expansion and persistence of chimeric antigen receptor (CAR) T cells correlate with therapeutic efficacy. However, properties of CAR T cells that enable their in vivo proliferation have still to be consistently defined and the role of CAR T bag content has never been investigated in a real-life setting. Experimental Design: Residual cells obtained after washing 61 anti-CD19 CAR T product bags were analyzed to identify tisagen-lecleucel/Tisa-cel and axicabtagene ciloleucel/Axi-cel phenotypic features associated with postinfusion CAR T-cell in vivo expansion and with response and survival. Results: While Tisa-cel was characterized by a significant enrichment in CAR thorn CD4 thorn T cells with central memory (P < 0.005) and effector (P < 0.005) phenotypes and lower rates of CAR thorn CD8 thorn with effector memory (P < 0.005) and naive-like (P < 0.05) phenotypes as compared with Axi-cel, the two products displayed similar expansion kinetics. In vivo CAR T-cell expansion was influenced by the presence of CAR T with a CD8 thorn T central memory signature (P < 0.005) in both Tisa-cel and Axi-cel infusion products and was positively associated with response and progression-free survival (P < 0.05). Conclusions: Our data indicate that despite the great heterogeneity of Tisa-cel and Axi-cel products, the differentiation status of the infused cells mediates CAR T-cell in vivo proliferation that is necessary for antitumor response.
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