Transposon-Based CAR T Cells in Acute Leukemias: Where Are We Going?
Open Access
- 26 May 2020
- Vol. 9 (6), 1337
- https://doi.org/10.3390/cells9061337
Abstract
Chimeric Antigen Receptor (CAR) T-cell therapy has become a new therapeutic reality for refractory and relapsed leukemia patients and is also emerging as a potential therapeutic option in solid tumors. Viral vector-based CAR T-cells initially drove these successful efforts; however, high costs and cumbersome manufacturing processes have limited the widespread clinical implementation of CAR T-cell therapy. Here we will discuss the state of the art of the transposon-based gene transfer and its application in CAR T immunotherapy, specifically focusing on the Sleeping Beauty (SB) transposon system, as a valid cost-effective and safe option as compared to the viral vector-based systems. A general overview of SB transposon system applications will be provided, with an update of major developments, current clinical trials achievements and future perspectives exploiting SB for CAR T-cell engineering. After the first clinical successes achieved in the context of B-cell neoplasms, we are now facing a new era and it is paramount to advance gene transfer technology to fully exploit the potential of CAR T-cells towards next-generation immunotherapy.This publication has 95 references indexed in Scilit:
- Manufacture of Clinical-Grade CD19-Specific T Cells Stably Expressing Chimeric Antigen Receptor Using Sleeping Beauty System and Artificial Antigen Presenting CellsPLOS ONE, 2013
- Advances in graft-versus-host disease biology and therapyNature Reviews Immunology, 2012
- Simplified Method of the Growth of Human Tumor Infiltrating Lymphocytes in Gas-permeable Flasks to Numbers Needed for Patient TreatmentJournal of Immunotherapy, 2012
- Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid LeukemiaThe New England Journal of Medicine, 2011
- Reprogramming CD19-Specific T Cells with IL-21 Signaling Can Improve Adoptive Immunotherapy of B-Lineage MalignanciesCancer Research, 2011
- A Transposon and Transposase System for Human ApplicationMolecular Therapy, 2010
- Efficient Human Hematopoietic Cell Transduction Using RD114- and GALV-Pseudotyped Retroviral Vectors Produced in Suspension and Serum-Free MediaHuman Gene Therapy, 2009
- Efficient construction of producer cell lines for a SIN lentiviral vector for SCID-X1 gene therapy by concatemeric array transfectionBlood, 2009
- Redirecting Specificity of T-Cell Populations For CD19 Using the Sleeping Beauty SystemCancer Research, 2008
- piggyBac is a flexible and highly active transposon as compared to Sleeping Beauty , Tol2 , and Mos1 in mammalian cellsProceedings of the National Academy of Sciences of the United States of America, 2006