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Suicide Gene Therapy to Increase the Safety of Chimeric Antigen Receptor-Redirected T Lymphocytes

Chimeric antigen receptors (CARs) are generated by fusing the antigen-binding motif of a monoclonal antibody (mAb) with the signal transduction machinery of the T-cell receptor (TCR). The genetic modification of T lymphocytes with chimeric receptors specific for tumor-associated antigens (TAAs) allo...

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Autores principales: Casucci, Monica, Bondanza, Attilio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133962/
https://www.ncbi.nlm.nih.gov/pubmed/21750689
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author Casucci, Monica
Bondanza, Attilio
author_facet Casucci, Monica
Bondanza, Attilio
author_sort Casucci, Monica
collection PubMed
description Chimeric antigen receptors (CARs) are generated by fusing the antigen-binding motif of a monoclonal antibody (mAb) with the signal transduction machinery of the T-cell receptor (TCR). The genetic modification of T lymphocytes with chimeric receptors specific for tumor-associated antigens (TAAs) allows for the redirection towards tumor cells. Clinical experience with CAR-redirected T cells suggests that antitumor efficacy associates with some degree of toxicity, especially when TAA expression is shared with healthy tissues. This situation closely resembles the case of allogeneic hematopoietic stem cell transplantation (HSCT), wherein allorecognition causes both the graft-versus-leukemia (GVL) effect and graft-versus-host disease (GVHD). Suicide gene therapy, i.e. the genetic induction of a conditional suicide phenotype into donor T cells, enables dissociating the GVL effect from GVHD. Applying suicide gene modification to CAR-redirected T cells may therefore greatly increase their safety profile and facilitate their clinical development.
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spelling pubmed-31339622011-07-12 Suicide Gene Therapy to Increase the Safety of Chimeric Antigen Receptor-Redirected T Lymphocytes Casucci, Monica Bondanza, Attilio J Cancer Mini-Review Chimeric antigen receptors (CARs) are generated by fusing the antigen-binding motif of a monoclonal antibody (mAb) with the signal transduction machinery of the T-cell receptor (TCR). The genetic modification of T lymphocytes with chimeric receptors specific for tumor-associated antigens (TAAs) allows for the redirection towards tumor cells. Clinical experience with CAR-redirected T cells suggests that antitumor efficacy associates with some degree of toxicity, especially when TAA expression is shared with healthy tissues. This situation closely resembles the case of allogeneic hematopoietic stem cell transplantation (HSCT), wherein allorecognition causes both the graft-versus-leukemia (GVL) effect and graft-versus-host disease (GVHD). Suicide gene therapy, i.e. the genetic induction of a conditional suicide phenotype into donor T cells, enables dissociating the GVL effect from GVHD. Applying suicide gene modification to CAR-redirected T cells may therefore greatly increase their safety profile and facilitate their clinical development. Ivyspring International Publisher 2011-07-01 /pmc/articles/PMC3133962/ /pubmed/21750689 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
spellingShingle Mini-Review
Casucci, Monica
Bondanza, Attilio
Suicide Gene Therapy to Increase the Safety of Chimeric Antigen Receptor-Redirected T Lymphocytes
title Suicide Gene Therapy to Increase the Safety of Chimeric Antigen Receptor-Redirected T Lymphocytes
title_full Suicide Gene Therapy to Increase the Safety of Chimeric Antigen Receptor-Redirected T Lymphocytes
title_fullStr Suicide Gene Therapy to Increase the Safety of Chimeric Antigen Receptor-Redirected T Lymphocytes
title_full_unstemmed Suicide Gene Therapy to Increase the Safety of Chimeric Antigen Receptor-Redirected T Lymphocytes
title_short Suicide Gene Therapy to Increase the Safety of Chimeric Antigen Receptor-Redirected T Lymphocytes
title_sort suicide gene therapy to increase the safety of chimeric antigen receptor-redirected t lymphocytes
topic Mini-Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133962/
https://www.ncbi.nlm.nih.gov/pubmed/21750689
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