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Preclinical Characterization of a Novel Monoclonal Antibody NEO-201 for the Treatment of Human Carcinomas
NEO-201 is a novel humanized IgG1 monoclonal antibody that was derived from an immunogenic preparation of tumor-associated antigens from pooled allogeneic colon tumor tissue extracts. It was found to react against a variety of cultured human carcinoma cell lines and was highly reactive against the m...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758533/ https://www.ncbi.nlm.nih.gov/pubmed/29354121 http://dx.doi.org/10.3389/fimmu.2017.01899 |
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author | Fantini, Massimo David, Justin M. Saric, Olga Dubeykovskiy, Alexander Cui, Yongzhi Mavroukakis, Sharon A. Bristol, Andrew Annunziata, Christina M. Tsang, Kwong Y. Arlen, Philip M. |
author_facet | Fantini, Massimo David, Justin M. Saric, Olga Dubeykovskiy, Alexander Cui, Yongzhi Mavroukakis, Sharon A. Bristol, Andrew Annunziata, Christina M. Tsang, Kwong Y. Arlen, Philip M. |
author_sort | Fantini, Massimo |
collection | PubMed |
description | NEO-201 is a novel humanized IgG1 monoclonal antibody that was derived from an immunogenic preparation of tumor-associated antigens from pooled allogeneic colon tumor tissue extracts. It was found to react against a variety of cultured human carcinoma cell lines and was highly reactive against the majority of tumor tissues from many different carcinomas, including colon, pancreatic, stomach, lung, and breast cancers. NEO-201 also exhibited tumor specificity, as the majority of normal tissues were not recognized by this antibody. Functional assays revealed that treatment with NEO-201 is capable of mediating both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against tumor cells. Furthermore, the growth of human pancreatic xenograft tumors in vivo was largely attenuated by treatment with NEO-201 both alone and in combination with human peripheral blood mononuclear cells as an effector cell source for ADCC. In vivo biodistribution studies in human tumor xenograft-bearing mice revealed that NEO-201 preferentially accumulates in the tumor but not organ tissue. Finally, a single-dose toxicity study in non-human primates demonstrated safety and tolerability of NEO-201, as a transient decrease in circulating neutrophils was the only related adverse effect observed. These findings indicate that NEO-201 warrants clinical testing as both a novel diagnostic and therapeutic agent for the treatment of a broad variety of carcinomas. |
format | Online Article Text |
id | pubmed-5758533 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57585332018-01-19 Preclinical Characterization of a Novel Monoclonal Antibody NEO-201 for the Treatment of Human Carcinomas Fantini, Massimo David, Justin M. Saric, Olga Dubeykovskiy, Alexander Cui, Yongzhi Mavroukakis, Sharon A. Bristol, Andrew Annunziata, Christina M. Tsang, Kwong Y. Arlen, Philip M. Front Immunol Immunology NEO-201 is a novel humanized IgG1 monoclonal antibody that was derived from an immunogenic preparation of tumor-associated antigens from pooled allogeneic colon tumor tissue extracts. It was found to react against a variety of cultured human carcinoma cell lines and was highly reactive against the majority of tumor tissues from many different carcinomas, including colon, pancreatic, stomach, lung, and breast cancers. NEO-201 also exhibited tumor specificity, as the majority of normal tissues were not recognized by this antibody. Functional assays revealed that treatment with NEO-201 is capable of mediating both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against tumor cells. Furthermore, the growth of human pancreatic xenograft tumors in vivo was largely attenuated by treatment with NEO-201 both alone and in combination with human peripheral blood mononuclear cells as an effector cell source for ADCC. In vivo biodistribution studies in human tumor xenograft-bearing mice revealed that NEO-201 preferentially accumulates in the tumor but not organ tissue. Finally, a single-dose toxicity study in non-human primates demonstrated safety and tolerability of NEO-201, as a transient decrease in circulating neutrophils was the only related adverse effect observed. These findings indicate that NEO-201 warrants clinical testing as both a novel diagnostic and therapeutic agent for the treatment of a broad variety of carcinomas. Frontiers Media S.A. 2018-01-04 /pmc/articles/PMC5758533/ /pubmed/29354121 http://dx.doi.org/10.3389/fimmu.2017.01899 Text en Copyright © 2018 Fantini, David, Saric, Dubeykovskiy, Cui, Mavroukakis, Bristol, Annunziata, Tsang and Arlen. 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 Fantini, Massimo David, Justin M. Saric, Olga Dubeykovskiy, Alexander Cui, Yongzhi Mavroukakis, Sharon A. Bristol, Andrew Annunziata, Christina M. Tsang, Kwong Y. Arlen, Philip M. Preclinical Characterization of a Novel Monoclonal Antibody NEO-201 for the Treatment of Human Carcinomas |
title | Preclinical Characterization of a Novel Monoclonal Antibody NEO-201 for the Treatment of Human Carcinomas |
title_full | Preclinical Characterization of a Novel Monoclonal Antibody NEO-201 for the Treatment of Human Carcinomas |
title_fullStr | Preclinical Characterization of a Novel Monoclonal Antibody NEO-201 for the Treatment of Human Carcinomas |
title_full_unstemmed | Preclinical Characterization of a Novel Monoclonal Antibody NEO-201 for the Treatment of Human Carcinomas |
title_short | Preclinical Characterization of a Novel Monoclonal Antibody NEO-201 for the Treatment of Human Carcinomas |
title_sort | preclinical characterization of a novel monoclonal antibody neo-201 for the treatment of human carcinomas |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758533/ https://www.ncbi.nlm.nih.gov/pubmed/29354121 http://dx.doi.org/10.3389/fimmu.2017.01899 |
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