Targeting CD33 in chemoresistant AML patient-derived xenografts by CAR-CIK cells modified with an improved SB transposon system

Tools

Item Type:	Article
Title:	Targeting CD33 in chemoresistant AML patient-derived xenografts by CAR-CIK cells modified with an improved SB transposon system
Creators Name:	Rotiroti, M.C., Buracchi, C., Arcangeli, S., Galimberti, S., Valsecchi, M.G., Perriello, V.M., Rasko, T., Alberti, G., Magnani, C.F., Cappuzzello, C., Lundberg, F., Pande, A., Dastoli, G., Introna, M., Serafini, M., Biagi, E., Izsvák, Z., Biondi, A. and Tettamanti, S.
Abstract:	The successful implementation of chimeric antigen receptor (CAR)-T cell therapy in the clinical context of B cell malignancies has paved the way for further development in the more critical setting of acute myeloid leukemia (AML). Among the potentially targetable AML antigens, CD33 is insofar one of the main validated molecules. Here, we describe the feasibility of engineering cytokine-induced killer (CIK) cells with a CD33.CAR by using the latest optimized version of the non-viral Sleeping Beauty (SB) transposon system "SB100X-pT4." This offers the advantage of improving CAR expression on CIK cells, while reducing the amount of DNA transposase as compared to the previously employed "SB11-pT" version. SB-modified CD33.CAR-CIK cells exhibited significant antileukemic activity in vitro and in vivo in patient-derived AML xenograft models, reducing AML development when administered as an "early treatment" and delaying AML progression in mice with established disease. Notably, by exploiting an already optimized xenograft chemotherapy model that mimics human induction therapy in mice, we demonstrated for the first time that CD33.CAR-CIK cells are also effective toward chemotherapy resistant/residual AML cells, further supporting its future clinical development and implementation within the current standard regimens.
Keywords:	AML, CAR, CD33, Non-Viral Gene Transfer, Sleeping Beauty Transposon, Cytokine-Induced Killer Cells, Immunotherapy, Animals, Mice
Source:	Molecular Therapy
ISSN:	1525-0016
Publisher:	Cell Press
Volume:	28
Number:	9
Page Range:	1974-1986
Date:	2 September 2020
Additional Information:	Copyright © 2020 The American Society of Gene and Cell Therapy.
Official Publication:	https://doi.org/10.1016/j.ymthe.2020.05.021
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

Repository Staff Only: item control page