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Comprehensive Identification of Tumor-associated Antigens via Isolation of Human Monoclonal Antibodies that may be Therapeutic

Although the success of trastuzumab and rituximab for treatment of breast cancer and non-Hodgkins lymphoma, respectively, suggests that monoclonal antibodies (mAbs) will become important therapeutic agents against a wider range of cancers, useful therapeutic Abs are not yet available for the majorit...

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Detalles Bibliográficos
Autor principal: Kurosawa, Yoshikazu
Formato: Texto
Lenguaje:English
Publicado: The Korean Association of Immunobiologists 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803294/
https://www.ncbi.nlm.nih.gov/pubmed/20107531
http://dx.doi.org/10.4110/in.2009.9.1.4
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author Kurosawa, Yoshikazu
author_facet Kurosawa, Yoshikazu
author_sort Kurosawa, Yoshikazu
collection PubMed
description Although the success of trastuzumab and rituximab for treatment of breast cancer and non-Hodgkins lymphoma, respectively, suggests that monoclonal antibodies (mAbs) will become important therapeutic agents against a wider range of cancers, useful therapeutic Abs are not yet available for the majority of the human cancers because of our lack of knowledge of which antigens (Ags) are likely to become useful targets. We established a procedure for comprehensive identification of such Ags through the extensive isolation of human mAbs that may be therapeutic. Using the phage-display Ab library we isolated a large number of human mAbs that bind to the surface of tumor cells. They were individually screened by immunostaining, and clones that preferentially and strongly stained the malignant cells were chosen. The Ags recognized by those clones were isolated by immunoprecipitation and identified by mass spectrometry (MS). We isolated 2,114 mAbs with unique sequences and identified 25 distinct Ags highly expressed on several carcinomas. Of those 2,114 mAbs 434 bound to specifically to one of the 25 Ags. I am going to discuss how we could select proper target Ags for therapeutic Abs and candidate clones as therapeutic agents.
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spelling pubmed-28032942010-01-27 Comprehensive Identification of Tumor-associated Antigens via Isolation of Human Monoclonal Antibodies that may be Therapeutic Kurosawa, Yoshikazu Immune Netw Review Article Although the success of trastuzumab and rituximab for treatment of breast cancer and non-Hodgkins lymphoma, respectively, suggests that monoclonal antibodies (mAbs) will become important therapeutic agents against a wider range of cancers, useful therapeutic Abs are not yet available for the majority of the human cancers because of our lack of knowledge of which antigens (Ags) are likely to become useful targets. We established a procedure for comprehensive identification of such Ags through the extensive isolation of human mAbs that may be therapeutic. Using the phage-display Ab library we isolated a large number of human mAbs that bind to the surface of tumor cells. They were individually screened by immunostaining, and clones that preferentially and strongly stained the malignant cells were chosen. The Ags recognized by those clones were isolated by immunoprecipitation and identified by mass spectrometry (MS). We isolated 2,114 mAbs with unique sequences and identified 25 distinct Ags highly expressed on several carcinomas. Of those 2,114 mAbs 434 bound to specifically to one of the 25 Ags. I am going to discuss how we could select proper target Ags for therapeutic Abs and candidate clones as therapeutic agents. The Korean Association of Immunobiologists 2009-02 2009-02-28 /pmc/articles/PMC2803294/ /pubmed/20107531 http://dx.doi.org/10.4110/in.2009.9.1.4 Text en Copyright © 2009 The Korean Association of Immunobiologists http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Kurosawa, Yoshikazu
Comprehensive Identification of Tumor-associated Antigens via Isolation of Human Monoclonal Antibodies that may be Therapeutic
title Comprehensive Identification of Tumor-associated Antigens via Isolation of Human Monoclonal Antibodies that may be Therapeutic
title_full Comprehensive Identification of Tumor-associated Antigens via Isolation of Human Monoclonal Antibodies that may be Therapeutic
title_fullStr Comprehensive Identification of Tumor-associated Antigens via Isolation of Human Monoclonal Antibodies that may be Therapeutic
title_full_unstemmed Comprehensive Identification of Tumor-associated Antigens via Isolation of Human Monoclonal Antibodies that may be Therapeutic
title_short Comprehensive Identification of Tumor-associated Antigens via Isolation of Human Monoclonal Antibodies that may be Therapeutic
title_sort comprehensive identification of tumor-associated antigens via isolation of human monoclonal antibodies that may be therapeutic
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803294/
https://www.ncbi.nlm.nih.gov/pubmed/20107531
http://dx.doi.org/10.4110/in.2009.9.1.4
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