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Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates.

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Title: Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates.
Authors: Spring, Bryan Q.1, Abu-Yousif, Adnan O.1, Palanisami, Akilan1, Rizvi, Imran1, Xiang Zheng1, Zhiming Mai1, Anbil, Sriram1, Sears, R. Bryan1, Mensah, Lawrence B.1, Goldschmidt, Ruth1, Erdem, S. Sibel1, Oliva, Esther2, Hasan, Tayyaba1,3,4 thasan@mgh.harvard.edu
Source: Proceedings of the National Academy of Sciences of the United States of America. 3/11/2014, Vol. 111 Issue 10, pE933-E942. 10p.
Subjects: Cancer treatment, Metastasis, Antibody-toxin conjugates, Cancer cells, Chromophores, Fluorescence microscopy
Abstract: Drug-resistant micrometastases that escape standard therapies often go undetected until the emergence of lethal recurrent disease. Here, we show that it is possible to treat microscopic tumors selectively using an activatable immunoconjugate. The immunoconjugate is composed of self-quenching, near-infrared chromophores loaded onto a cancer cell-targeting antibody. Chromophore phototoxicity and fluorescence are activated by lysosomal proteolysis, and light, after cancer cell internalization, enabling tumor-confined photocytotoxicity and resolution of individual micrometastases. This unique approach not only introduces a therapeutic strategy to help destroy residual drug-resistant cells but also provides a sensitive imaging method to monitor micrometastatic disease in common sites of recurrence. Using fluorescence microendoscopy to monitor immunoconjugate activation and micrometastatic disease, we demonstrate these concepts of "tumor-targeted, activatable photoimmunotherapy" in a mouse model of peritoneal carcinomatosis. By introducing targeted activation to enhance tumor selectively in complex anatomical sites, this study offers prospects for catching early recurrent micrometastases and for treating occult disease. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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DbLabel: Engineering Source
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PubType: Academic Journal
PubTypeId: academicJournal
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  Data: Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates.
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  Data: <searchLink fieldCode="AR" term="%22Spring%2C+Bryan+Q%2E%22">Spring, Bryan Q.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Abu-Yousif%2C+Adnan+O%2E%22">Abu-Yousif, Adnan O.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Palanisami%2C+Akilan%22">Palanisami, Akilan</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Rizvi%2C+Imran%22">Rizvi, Imran</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Xiang+Zheng%22">Xiang Zheng</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Zhiming+Mai%22">Zhiming Mai</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Anbil%2C+Sriram%22">Anbil, Sriram</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Sears%2C+R%2E+Bryan%22">Sears, R. Bryan</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Mensah%2C+Lawrence+B%2E%22">Mensah, Lawrence B.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Goldschmidt%2C+Ruth%22">Goldschmidt, Ruth</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Erdem%2C+S%2E+Sibel%22">Erdem, S. Sibel</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Oliva%2C+Esther%22">Oliva, Esther</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Hasan%2C+Tayyaba%22">Hasan, Tayyaba</searchLink><relatesTo>1,3,4</relatesTo><i> thasan@mgh.harvard.edu</i>
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  Data: Drug-resistant micrometastases that escape standard therapies often go undetected until the emergence of lethal recurrent disease. Here, we show that it is possible to treat microscopic tumors selectively using an activatable immunoconjugate. The immunoconjugate is composed of self-quenching, near-infrared chromophores loaded onto a cancer cell-targeting antibody. Chromophore phototoxicity and fluorescence are activated by lysosomal proteolysis, and light, after cancer cell internalization, enabling tumor-confined photocytotoxicity and resolution of individual micrometastases. This unique approach not only introduces a therapeutic strategy to help destroy residual drug-resistant cells but also provides a sensitive imaging method to monitor micrometastatic disease in common sites of recurrence. Using fluorescence microendoscopy to monitor immunoconjugate activation and micrometastatic disease, we demonstrate these concepts of "tumor-targeted, activatable photoimmunotherapy" in a mouse model of peritoneal carcinomatosis. By introducing targeted activation to enhance tumor selectively in complex anatomical sites, this study offers prospects for catching early recurrent micrometastases and for treating occult disease. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1073/pnas.1319493111
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