{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T08:42:47Z","timestamp":1778056967775,"version":"3.51.4"},"reference-count":180,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T00:00:00Z","timestamp":1597968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["15\/26580-9"],"award-info":[{"award-number":["15\/26580-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2019s, 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.<\/jats:p>","DOI":"10.3390\/cancers12092360","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T21:13:42Z","timestamp":1597958022000},"page":"2360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Overhauling CAR T Cells to Improve Efficacy, Safety and Cost"],"prefix":"10.3390","volume":"12","author":[{"given":"Leonardo","family":"Chicaybam","sequence":"first","affiliation":[{"name":"Vice Presid\u00eancia de Pesquisa e Cole\u00e7\u00f5es Biol\u00f3gicas, Funda\u00e7\u00e3o Instituto Oswaldo Cruz (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"},{"name":"Programa de Imunologia e Biologia de Tumores, Coordena\u00e7\u00e3o de Pesquisa, Instituto Nacional de C\u00e2ncer (INCA), Rio de Janeiro 20231-050, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4416-5822","authenticated-orcid":false,"given":"Mart\u00edn H.","family":"Bonamino","sequence":"additional","affiliation":[{"name":"Vice Presid\u00eancia de Pesquisa e Cole\u00e7\u00f5es Biol\u00f3gicas, Funda\u00e7\u00e3o Instituto Oswaldo Cruz (FIOCRUZ), Rio de Janeiro 21040-900, Brazil"},{"name":"Programa de Imunologia e Biologia de Tumores, Coordena\u00e7\u00e3o de Pesquisa, Instituto Nacional de C\u00e2ncer (INCA), Rio de Janeiro 20231-050, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Luckow Invitti","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Federal University of S\u00e3o Paulo\u2013Escola Paulista de Medicina (UNIFESP-EPM); Colsan Beneficial Blood Collection Association, S\u00e3o Paulo 04039-032, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7890-573X","authenticated-orcid":false,"given":"Patricia","family":"Bortman Rozenchan","sequence":"additional","affiliation":[{"name":"Celluris, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"de Luna Vieira","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o Translacional em Oncologia, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4113-9450","authenticated-orcid":false,"given":"Bryan E.","family":"Strauss","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o Translacional em Oncologia, Instituto do C\u00e2ncer do Estado de S\u00e3o Paulo, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,21]]},"reference":[{"key":"ref_1","unstructured":"(2020, August 11). 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