Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer
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Author(s)
Lauffer, Sam
Matulonis, Ursula
Pepin, David
Birrer, Michael J.
Qi, Ruogu
Wang, Yongheng
Bruno, Peter Michael
Xiao, Haihua
Yu, Yingjie
Li, Ting
Date Issued
December 2017
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Qi, Ruogu et al. “Nanoparticle Conjugates of a Highly Potent Toxin Enhance Safety and Circumvent Platinum Resistance in Ovarian Cancer.” Nature Communications 8, 1 (December 2017): 2166 © 2017 The Author(s)
Version
Final published version
Abstract
Advanced-stage epithelial ovarian cancers are amongst the most difficult to treat tumors and have proven to be refractory to most cytotoxic, molecularly targeted, or immunotherapeutic approaches. Here, we report that nanoparticle-drug conjugates (NDCs) of monomethyl auristatin E (MMAE) significantly increase loading on a per-vehicle basis as compared to antibody-drug conjugates (ADCs). Their intraperitoneal administration enabled triggered release of the active MMAE toxin to inhibit tumor growth and to extend animal survival to > 90 days in a cell-line xenograft model of disseminated ovarian cancer. In a patient-derived xenograft model of advanced-stage and platinum-resistant ovarian cancer, an MMAE-based NDC doubled the duration of tumor growth inhibition as compared to cisplatin. NDCs of highly potent toxins thus introduce a translatable platform that may be exploited to maximize the safety and efficacy of cytotoxic chemotherapies, combining the best features of ADCs with those of nanoparticle-based therapeutics.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/s41467-017-02390-7
