Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates
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Spring-2014-Selective treatment.pdf
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Author(s)
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
Date Issued
February 2014
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
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.
Version
Final published version
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
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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.
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DOI of Published Version
https://doi.org/10.1073/pnas.1319493111
