Phenotypic Composition of Commercial Anti-CD19 CAR T Cells Affects In Vivo Expansion and Disease Response in Patients with Large B-cell Lymphoma.
Clin Cancer Res
; 28(15): 3378-3386, 2022 08 02.
Article
in En
| MEDLINE
| ID: mdl-35583610
ABSTRACT
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. EXPERIMENTALDESIGN:
Residual cells obtained after washing 61 anti-CD19 CAR T product bags were analyzed to identify tisagenlecleucel/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+CD4+ T cells with central memory (P < 0.005) and effector (P < 0.005) phenotypes and lower rates of CAR+CD8+ with effector memory (P < 0.005) and naïve-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+ 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphoma, Large B-Cell, Diffuse
/
Receptors, Chimeric Antigen
Limits:
Humans
Language:
En
Journal:
Clin Cancer Res
Journal subject:
NEOPLASIAS
Year:
2022
Document type:
Article
Affiliation country:
Italy