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Novel Immunocytokine IL12-SS1 (Fv) Inhibits Mesothelioma Tumor Growth in Nude Mice

Mesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of malignant mesothelioma. Monoclonal antibodies against mesothelin are being evaluated for the treatment of mesothelioma. Immunocytokines represent a novel class of armed antibodies. To p...

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Autores principales: Kim, Heungnam, Gao, Wei, Ho, Mitchell
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829959/
https://www.ncbi.nlm.nih.gov/pubmed/24260587
http://dx.doi.org/10.1371/journal.pone.0081919
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author Kim, Heungnam
Gao, Wei
Ho, Mitchell
author_facet Kim, Heungnam
Gao, Wei
Ho, Mitchell
author_sort Kim, Heungnam
collection PubMed
description Mesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of malignant mesothelioma. Monoclonal antibodies against mesothelin are being evaluated for the treatment of mesothelioma. Immunocytokines represent a novel class of armed antibodies. To provide an alternative approach to current mesothelin-targeted antibody therapies, we have developed a novel immunocytokine based on interleukin-12 (IL12) and the SS1 Fv specific for mesothelin. IL12 possesses potent anti-tumor activity in a wide variety of solid tumors. The newly-developed recombinant immunocytokine, IL12-SS1 (Fv), was produced in insect cells using a baculovirus-insect cell expression system. The SS1 single-chain Fv was fused to the C terminus of the p35 subunit of IL12 through a short linker (GSADGG). The single-chain IL12-SS1 (Fv) immunocytokine bound native mesothelin proteins on malignant mesothelioma (NCI-H226) and ovarian (OVCAR-3) cells as well as recombinant mesothelin on A431/H9 cells. The immunocytokine retained sufficient bioactivity of IL12 and significantly inhibited human malignant mesothelioma (NCI-H226) grown in the peritoneal cavity of nude mice and showed comparable anti-tumor activity to that of the SS1P immunotoxin. IL12-SS1 (Fv) is the first reported immunocytokine to mesothelin-positive tumors and may be an attractive addition to mesothelin-targeted cancer therapies.
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spelling pubmed-38299592013-11-20 Novel Immunocytokine IL12-SS1 (Fv) Inhibits Mesothelioma Tumor Growth in Nude Mice Kim, Heungnam Gao, Wei Ho, Mitchell PLoS One Research Article Mesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of malignant mesothelioma. Monoclonal antibodies against mesothelin are being evaluated for the treatment of mesothelioma. Immunocytokines represent a novel class of armed antibodies. To provide an alternative approach to current mesothelin-targeted antibody therapies, we have developed a novel immunocytokine based on interleukin-12 (IL12) and the SS1 Fv specific for mesothelin. IL12 possesses potent anti-tumor activity in a wide variety of solid tumors. The newly-developed recombinant immunocytokine, IL12-SS1 (Fv), was produced in insect cells using a baculovirus-insect cell expression system. The SS1 single-chain Fv was fused to the C terminus of the p35 subunit of IL12 through a short linker (GSADGG). The single-chain IL12-SS1 (Fv) immunocytokine bound native mesothelin proteins on malignant mesothelioma (NCI-H226) and ovarian (OVCAR-3) cells as well as recombinant mesothelin on A431/H9 cells. The immunocytokine retained sufficient bioactivity of IL12 and significantly inhibited human malignant mesothelioma (NCI-H226) grown in the peritoneal cavity of nude mice and showed comparable anti-tumor activity to that of the SS1P immunotoxin. IL12-SS1 (Fv) is the first reported immunocytokine to mesothelin-positive tumors and may be an attractive addition to mesothelin-targeted cancer therapies. Public Library of Science 2013-11-15 /pmc/articles/PMC3829959/ /pubmed/24260587 http://dx.doi.org/10.1371/journal.pone.0081919 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Kim, Heungnam
Gao, Wei
Ho, Mitchell
Novel Immunocytokine IL12-SS1 (Fv) Inhibits Mesothelioma Tumor Growth in Nude Mice
title Novel Immunocytokine IL12-SS1 (Fv) Inhibits Mesothelioma Tumor Growth in Nude Mice
title_full Novel Immunocytokine IL12-SS1 (Fv) Inhibits Mesothelioma Tumor Growth in Nude Mice
title_fullStr Novel Immunocytokine IL12-SS1 (Fv) Inhibits Mesothelioma Tumor Growth in Nude Mice
title_full_unstemmed Novel Immunocytokine IL12-SS1 (Fv) Inhibits Mesothelioma Tumor Growth in Nude Mice
title_short Novel Immunocytokine IL12-SS1 (Fv) Inhibits Mesothelioma Tumor Growth in Nude Mice
title_sort novel immunocytokine il12-ss1 (fv) inhibits mesothelioma tumor growth in nude mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829959/
https://www.ncbi.nlm.nih.gov/pubmed/24260587
http://dx.doi.org/10.1371/journal.pone.0081919
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