Modified Manufacturing Process Modulates CD19CAR T-cell Engraftment Fitness and Leukemia-Free Survival in Pediatric and Young Adult Subjects.
Details
Serval ID
serval:BIB_FC5F316AD054
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Modified Manufacturing Process Modulates CD19CAR T-cell Engraftment Fitness and Leukemia-Free Survival in Pediatric and Young Adult Subjects.
Journal
Cancer immunology research
ISSN
2326-6074 (Electronic)
ISSN-L
2326-6066
Publication state
Published
Issued date
01/07/2022
Peer-reviewed
Oui
Volume
10
Number
7
Pages
856-870
Language
english
Notes
Publication types: Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
Publication Status: ppublish
Publication Status: ppublish
Abstract
T cells modified to express a chimeric antigen receptor (CAR) targeting CD19 can induce potent and sustained responses in children with relapsed/refractory acute lymphoblastic leukemia (ALL). The durability of remission is related to the length of time the CAR T cells persist. Efforts to understand differences in persistence have focused on the CAR construct, in particular the costimulatory signaling module of the chimeric receptor. We previously reported a robust intent-to-treat product manufacturing success rate and remission induction rate in children and young adults with recurrent/refractory B-ALL using the SCRI-CAR19v1 product, a second-generation CD19-specific CAR with 4-1BB costimulation coexpressed with the EGFRt cell-surface tag (NCT02028455). Following completion of the phase I study, two changes to CAR T-cell manufacturing were introduced: switching the T-cell activation reagent and omitting midculture EGFRt immunomagnetic selection. We tested the modified manufacturing process and resulting product, designated SCRI-CAR19v2, in a cohort of 21 subjects on the phase II arm of the trial. Here, we describe the unanticipated enhancement in product performance resulting in prolonged persistence and B-cell aplasia and improved leukemia-free survival with SCRI-CAR19v2 as compared with SCRI-CAR19v1.
Keywords
Antigens, CD19, Child, Clinical Trials, Phase I as Topic, Humans, Immunotherapy, Adoptive/methods, Lymphoma, B-Cell, Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy, Receptors, Antigen, T-Cell/genetics, Receptors, Chimeric Antigen/genetics, Recurrence, T-Lymphocytes, Young Adult
Pubmed
Web of science
Create date
23/05/2022 12:31
Last modification date
15/08/2023 6:00