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Overhauling CAR T Cells to Improve Efficacy, Safety and Cost

1
Vice Presidência de Pesquisa e Coleções Biológicas, Fundação Instituto Oswaldo Cruz (FIOCRUZ), Rio de Janeiro 21040-900, Brazil
2
Programa de Imunologia e Biologia de Tumores, Coordenação de Pesquisa, Instituto Nacional de Câncer (INCA), Rio de Janeiro 20231-050, Brazil
3
Department of Gynecology, Federal University of São Paulo–Escola Paulista de Medicina (UNIFESP-EPM); Colsan Beneficial Blood Collection Association, São Paulo 04039-032, Brazil
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Celluris, São Paulo 05508-000, Brazil
5
Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo 01246-000, Brazil
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(9), 2360; https://doi.org/10.3390/cancers12092360
Received: 6 July 2020 / Revised: 6 August 2020 / Accepted: 10 August 2020 / Published: 21 August 2020
(This article belongs to the Section Cancer Immunology and Immunotherapy)
Gene therapy is now surpassing 30 years of clinical experience and in that time a variety of approaches has been applied for the treatment of a wide range of pathologies. While the promise of gene therapy was over-stated in the 1990’s, the following decades were met with polar extremes between demonstrable success and devastating setbacks. Currently, the field of gene therapy is enjoying the rewards of overcoming the hurdles that come with turning new ideas into safe and reliable treatments, including for cancer. Among these modalities, the modification of T cells with chimeric antigen receptors (CAR-T cells) has met with clear success and holds great promise for the future treatment of cancer. We detail a series of considerations for the improvement of the CAR-T cell approach, including the design of the CAR, routes of gene transfer, introduction of CARs in natural killer and other cell types, combining the CAR approach with checkpoint blockade or oncolytic viruses, improving pre-clinical models as well as means for reducing cost and, thus, making this technology more widely available. While CAR-T cells serve as a prime example of translating novel ideas into effective treatments, certainly the lessons learned will serve to accelerate the current and future development of gene therapy drugs. View Full-Text
Keywords: gene therapy; chimeric antigen receptor; T cell; NK cell; cancer; immunotherapy gene therapy; chimeric antigen receptor; T cell; NK cell; cancer; immunotherapy
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Chicaybam, L.; Bonamino, M.H.; Luckow Invitti, A.; Bortman Rozenchan, P.; de Luna Vieira, I.; Strauss, B.E. Overhauling CAR T Cells to Improve Efficacy, Safety and Cost. Cancers 2020, 12, 2360.

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