James P. Crowley, Professor of Medicine emeritus at Brown University, shared a post by Miguel Bronchud, Co-Founder and Advisory Board at Regenerative Medicine Solutions, on LinkedIn, adding:
“Overall, 7 of the 11 patients (64%) who received the investigational therapy were in ongoing remission at 3 to 36 months after transplantation, and leukemia with loss of CD7 expression was documented in 2 patients.
Universal BE-CAR7 T cells induced leukemic remission in patients with relapsed or refractory T-cell ALL, thus allowing successful allogeneic hematopoietic stem-cell transplantation in most of the patients.”
Quoting Miguel Bronchud‘s post:
“Getting there? Gene editing and chimeric antigen receptors in T cells can now deal with dangerous Tcell lymphoblastic leukemia cells in some 70% of patients?
CAR T therapies (still undergoing development in solid tumors) have shown remarkable improvement in the survival outcome of patients (children and adults) with relapses of B cell acute lymphoblastic leukemia; but not particularly in T cell variants in children. This paper in the NEJM is excellent news for many children and parents:
Universal Base-Edited CAR7 T Cells for T-Cell Acute Lymphoblastic Leukemia
Switching out letters in the genetic code of CAR T cells has put 7 out of 11 people with a type of blood cancer known as acute lymphoblastic leukemia into remission.
The pioneering treatment uses CRISPR to make three base edits in the DNA of donor CAR T cells. These edits make it possible for the CAR T cells to seek out and destroy cancerous T cells while shielding themselves from attack from the immune system and chemotherapy. “A few years ago, this would have been science fiction,” says co-author and biomedical scientist Waseem Qasim.
Waseem Qasim can be contacted at Great Ormond Street Hospital for Children, 20 Guilford St., London WC1N 1DZ, United Kingdom.
CD7 is an attractive target for chimeric antigen receptor (CAR) T-cell therapy in relapsed or refractory T-cell acute lymphoblastic leukemia (ALL). Supportive results of first-in-human studies of base-edited anti-CD7 CAR (BE-CAR7) T cells with triple C→T deamination-mediated knockouts of TCRαβ, CD52, and CD7 have been reported previously.
In a phase 1 study, these International researchers coordinated from Great Ormond Street (“Peter Pan’s” children hospital in London) administered BE-CAR7 T cells to children (≤16 years of age) with relapsed or refractory T-cell ALL after they had undergone lymphodepletion with fludarabine, cyclophosphamide, and alemtuzumab.
Adults with compassionate-use access arrangements were also eligible. Patients who had remission by day 28 after the BE-CAR7 T-cell infusion proceeded to allogeneic hematopoietic stem-cell transplantation.
The primary outcome was safety. Secondary outcomes included duration of remission, disease-free survival, and overall survival.
BE-CAR7 T cells were administered to 9 children, as well as to 2 adults who were treated under compassionate-use access arrangements. Lymphodepletion and BE-CAR7 infusions did not lead to unacceptable adverse events, and circulating CAR7 T cells were detected in all the patients. Complications included cytokine release syndrome of grades 1 through 4, transient rashes, multilineage cytopenia, and opportunistic infections.
All the patients had complete morphologic remission with incomplete count recovery at day 28. 9 patients (82%) had deep remission (according to flow cytometry or PCR ) that allowed them to proceed to stem-cell transplantation.”
Title: Universal Base-Edited CAR7 T Cells for T-Cell Acute Lymphoblastic Leukemia
Authors: Robert Chiesa, Christos Georgiadis, Hebatalla Rashed, Roland Preece, Prudence Hardefeldt, Jan Chu, Jemma Selvage, Avijeet Mishra, Batoul Ahmed, Stuart Adams, Rebecca Thomas, Kimberly Gilmour, Annie Etuk, Deborah Yallop, David O’Connor, and Waseem Qasim
Read The Full Article on The New England Journal of Medicine.
More posts featuring Miguel Bronchud and James P. Crowley on OncoDaily.