Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates
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-i...
| Main Authors: | , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2014
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| Online Access: | http://hdl.handle.net/1721.1/90355 |
| _version_ | 1811079978617405440 |
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| author | Spring, Bryan Q. Abu-Yousif, Adnan O. Palanisami, Akilan Rizvi, Imran Zheng, Xiang Mai, Zhiming Anbil, Sriram Sears, R. Bryan Mensah, Lawrence B. Goldschmidt, Ruth Erdem, S. Sibel Oliva, Esther Hasan, Tayyaba |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Spring, Bryan Q. Abu-Yousif, Adnan O. Palanisami, Akilan Rizvi, Imran Zheng, Xiang Mai, Zhiming Anbil, Sriram Sears, R. Bryan Mensah, Lawrence B. Goldschmidt, Ruth Erdem, S. Sibel Oliva, Esther Hasan, Tayyaba |
| author_sort | Spring, Bryan Q. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:23:32Z |
| format | Article |
| id | mit-1721.1/90355 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:23:32Z |
| publishDate | 2014 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/903552022-09-27T19:13:47Z Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates Spring, Bryan Q. Abu-Yousif, Adnan O. Palanisami, Akilan Rizvi, Imran Zheng, Xiang Mai, Zhiming Anbil, Sriram Sears, R. Bryan Mensah, Lawrence B. Goldschmidt, Ruth Erdem, S. Sibel Oliva, Esther Hasan, Tayyaba Harvard University--MIT Division of Health Sciences and Technology Hasan, Tayyaba 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. National Science Foundation (U.S.) (R01-AR40352) National Science Foundation (U.S.) (RC1-CA146337) National Science Foundation (U.S.) (R01-CA160998) National Science Foundation (U.S.) (P01-CA084203) National Science Foundation (U.S.) (F32-CA144210) 2014-09-25T18:52:45Z 2014-09-25T18:52:45Z 2014-02 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/90355 Spring, B. Q., A. O. Abu-Yousif, A. Palanisami, I. Rizvi, X. Zheng, Z. Mai, S. Anbil, et al. “Selective Treatment and Monitoring of Disseminated Cancer Micrometastases in Vivo Using Dual-Function, Activatable Immunoconjugates.” Proceedings of the National Academy of Sciences 111, no. 10 (February 26, 2014): E933–E942. 24572574 en_US http://dx.doi.org/10.1073/pnas.1319493111 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) National Academy of Sciences (U.S.) |
| spellingShingle | Spring, Bryan Q. Abu-Yousif, Adnan O. Palanisami, Akilan Rizvi, Imran Zheng, Xiang Mai, Zhiming Anbil, Sriram Sears, R. Bryan Mensah, Lawrence B. Goldschmidt, Ruth Erdem, S. Sibel Oliva, Esther Hasan, Tayyaba Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates |
| title | Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates |
| title_full | Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates |
| title_fullStr | Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates |
| title_full_unstemmed | Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates |
| title_short | Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates |
| title_sort | selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual function activatable immunoconjugates |
| url | http://hdl.handle.net/1721.1/90355 |
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