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Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy

The remarkable progress in engineering and clinical development of therapeutic antibodies in the last 40 years, after the seminal work by Köhler and Milstein, has led to the approval by the United States Food and Drug Administration (FDA) of 21 antibodies for cancer immunotherapy. We review here the...

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Autores principales: Almagro, Juan C., Daniels-Wells, Tracy R., Perez-Tapia, Sonia Mayra, Penichet, Manuel L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770808/
https://www.ncbi.nlm.nih.gov/pubmed/29379493
http://dx.doi.org/10.3389/fimmu.2017.01751
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author Almagro, Juan C.
Daniels-Wells, Tracy R.
Perez-Tapia, Sonia Mayra
Penichet, Manuel L.
author_facet Almagro, Juan C.
Daniels-Wells, Tracy R.
Perez-Tapia, Sonia Mayra
Penichet, Manuel L.
author_sort Almagro, Juan C.
collection PubMed
description The remarkable progress in engineering and clinical development of therapeutic antibodies in the last 40 years, after the seminal work by Köhler and Milstein, has led to the approval by the United States Food and Drug Administration (FDA) of 21 antibodies for cancer immunotherapy. We review here these approved antibodies, with emphasis on the methods used for their discovery, engineering, and optimization for therapeutic settings. These methods include antibody engineering via chimerization and humanization of non-human antibodies, as well as selection and further optimization of fully human antibodies isolated from human antibody phage-displayed libraries and immunization of transgenic mice capable of generating human antibodies. These technology platforms have progressively led to the development of therapeutic antibodies with higher human content and, thus, less immunogenicity. We also discuss the genetic engineering approaches that have allowed isotype switching and Fc modifications to modulate effector functions and bioavailability (half-life), which together with the technologies for engineering the Fv fragment, have been pivotal in generating more efficacious and better tolerated therapeutic antibodies to treat cancer.
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spelling pubmed-57708082018-01-29 Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy Almagro, Juan C. Daniels-Wells, Tracy R. Perez-Tapia, Sonia Mayra Penichet, Manuel L. Front Immunol Immunology The remarkable progress in engineering and clinical development of therapeutic antibodies in the last 40 years, after the seminal work by Köhler and Milstein, has led to the approval by the United States Food and Drug Administration (FDA) of 21 antibodies for cancer immunotherapy. We review here these approved antibodies, with emphasis on the methods used for their discovery, engineering, and optimization for therapeutic settings. These methods include antibody engineering via chimerization and humanization of non-human antibodies, as well as selection and further optimization of fully human antibodies isolated from human antibody phage-displayed libraries and immunization of transgenic mice capable of generating human antibodies. These technology platforms have progressively led to the development of therapeutic antibodies with higher human content and, thus, less immunogenicity. We also discuss the genetic engineering approaches that have allowed isotype switching and Fc modifications to modulate effector functions and bioavailability (half-life), which together with the technologies for engineering the Fv fragment, have been pivotal in generating more efficacious and better tolerated therapeutic antibodies to treat cancer. Frontiers Media S.A. 2018-01-04 /pmc/articles/PMC5770808/ /pubmed/29379493 http://dx.doi.org/10.3389/fimmu.2017.01751 Text en Copyright © 2018 Almagro, Daniels-Wells, Perez-Tapia, and Penichet. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Almagro, Juan C.
Daniels-Wells, Tracy R.
Perez-Tapia, Sonia Mayra
Penichet, Manuel L.
Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy
title Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy
title_full Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy
title_fullStr Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy
title_full_unstemmed Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy
title_short Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy
title_sort progress and challenges in the design and clinical development of antibodies for cancer therapy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770808/
https://www.ncbi.nlm.nih.gov/pubmed/29379493
http://dx.doi.org/10.3389/fimmu.2017.01751
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