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Challenges of driving CD30-directed CAR-T cells to the clinic
Chimeric antigen receptor T (CAR-T) cells are a promising new treatment for patients with relapsed or refractory hematologic malignancies, including lymphoma. Given the success of CAR-T cells directed against CD19, new targets are being developed and tested, since not all lymphomas express CD19. CD3...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404322/ https://www.ncbi.nlm.nih.gov/pubmed/30841880 http://dx.doi.org/10.1186/s12885-019-5415-9 |
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author | Grover, Natalie S. Savoldo, Barbara |
author_facet | Grover, Natalie S. Savoldo, Barbara |
author_sort | Grover, Natalie S. |
collection | PubMed |
description | Chimeric antigen receptor T (CAR-T) cells are a promising new treatment for patients with relapsed or refractory hematologic malignancies, including lymphoma. Given the success of CAR-T cells directed against CD19, new targets are being developed and tested, since not all lymphomas express CD19. CD30 is promising target as it is universally expressed in virtually all classical Hodgkin lymphomas, anaplastic large cell lymphomas, and in a proportion of other lymphoma types, including cutaneous T cell lymphomas and diffuse large B cell lymphomas. Preclinical studies with CD30-directed CAR-T cells support the feasibility of this approach. Recently, two clinical trials of CD30-directed CAR-T cells in relapsed/refractory CD30+ lymphomas, including Hodgkin lymphoma, have been reported with minimal toxicities noted and preliminary efficacy seen in a proportion of patients. However, improving the persistence and expansion of CAR-T cells is key to further enhancing the efficacy of this treatment approach. Future directions include optimizing the lymphodepletion regimen, enhancing migration to the tumor site, and combination with other immune regulators. Several ongoing and upcoming clinical trials of CD30-directed CAR-T cells are expected to further enhance this approach to treat patients with relapsed and refractory CD30+ lymphomas. |
format | Online Article Text |
id | pubmed-6404322 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-64043222019-03-18 Challenges of driving CD30-directed CAR-T cells to the clinic Grover, Natalie S. Savoldo, Barbara BMC Cancer Review Chimeric antigen receptor T (CAR-T) cells are a promising new treatment for patients with relapsed or refractory hematologic malignancies, including lymphoma. Given the success of CAR-T cells directed against CD19, new targets are being developed and tested, since not all lymphomas express CD19. CD30 is promising target as it is universally expressed in virtually all classical Hodgkin lymphomas, anaplastic large cell lymphomas, and in a proportion of other lymphoma types, including cutaneous T cell lymphomas and diffuse large B cell lymphomas. Preclinical studies with CD30-directed CAR-T cells support the feasibility of this approach. Recently, two clinical trials of CD30-directed CAR-T cells in relapsed/refractory CD30+ lymphomas, including Hodgkin lymphoma, have been reported with minimal toxicities noted and preliminary efficacy seen in a proportion of patients. However, improving the persistence and expansion of CAR-T cells is key to further enhancing the efficacy of this treatment approach. Future directions include optimizing the lymphodepletion regimen, enhancing migration to the tumor site, and combination with other immune regulators. Several ongoing and upcoming clinical trials of CD30-directed CAR-T cells are expected to further enhance this approach to treat patients with relapsed and refractory CD30+ lymphomas. BioMed Central 2019-03-06 /pmc/articles/PMC6404322/ /pubmed/30841880 http://dx.doi.org/10.1186/s12885-019-5415-9 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Review Grover, Natalie S. Savoldo, Barbara Challenges of driving CD30-directed CAR-T cells to the clinic |
title | Challenges of driving CD30-directed CAR-T cells to the clinic |
title_full | Challenges of driving CD30-directed CAR-T cells to the clinic |
title_fullStr | Challenges of driving CD30-directed CAR-T cells to the clinic |
title_full_unstemmed | Challenges of driving CD30-directed CAR-T cells to the clinic |
title_short | Challenges of driving CD30-directed CAR-T cells to the clinic |
title_sort | challenges of driving cd30-directed car-t cells to the clinic |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404322/ https://www.ncbi.nlm.nih.gov/pubmed/30841880 http://dx.doi.org/10.1186/s12885-019-5415-9 |
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