Preclinical Evaluation of an Anti-CD41 CAR T Cell in Acute Megakaryoblastic Leukemia on in Vitro and In Vivo Models
Year: 2024
Type: article
Abstract: Acute Megakaryoblastic Leukemia (AMkL) is a rare disease that represents 5% of all reported AML cases and is diagnosed with high frequency in children with Down Syndrome and elderly people. M7-AMkL is characterized by a low overall survival and the patients have poor outcome to treatment, thus alternative treatments, such as CAR T cell therapies, are a need for better patient management. Herein, we present an evaluation of a new CAR T cell which targets CD41 marker, a specific surface antigen for M7-AMkL, in a preclinical model for AMkL using DAMI Luc2 cell line for in vitro and in vivo experiments. The performed flow cytometry evaluation showed that over 93% of the CAR T cells are eGFP positive, carrying the plasmid that permits CD41 targeting. The results highlight that the CAR T cells are inhibiting the AMkL cells with limited efficacy, with best inhibitory effect at lower effect: target ratios. The CAR T cells induced membrane damage to the targets, results sustained by the increased LDH activity, moreover TNF alpha levels were increased in the low E:T groups even after 24h. The in vivo evaluation indicates that the CAR T cells lowered the tumor size rapidly, but with limited efficacy due to the initiation of CRS. Our findings suggest that the anti CD41 CAR T cells are efficient for a limited time spawn and the better cytotoxic effect was visible in the low E:T ratio groups. However, further optimizations and evaluation are needed to improve the outcome of the anti CD41 CAR T cells.
Authors: Adrian Bogdan Tigu, Catalin Constantinescu, Patric Teodorescu, David Kegyes, Raluca Munteanu, Richard Feder, Mareike Peters, Ioana Pralea, Cristina Iuga, Diana Cenariu, Andra Marcu, Alina Daniela Tanase, Anca Colita, Rares Drula, Jon Thor Bergthorsson, Victor Greiff, Delia Dima, Cristina Selicean, Ioana Rus, Mihnea Zdrenghea, Diana Gulei, Gabriel Ghiaur, Ciprian Tomuleasa
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W4391603165