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Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer

Author

Listed:
  • Ruogu Qi

    (Koch Institute for Integrative Cancer Research at MIT)

  • Yongheng Wang

    (Koch Institute for Integrative Cancer Research at MIT)

  • Peter M. Bruno

    (Koch Institute for Integrative Cancer Research at MIT)

  • Haihua Xiao

    (Koch Institute for Integrative Cancer Research at MIT)

  • Yingjie Yu

    (Koch Institute for Integrative Cancer Research at MIT)

  • Ting Li

    (Koch Institute for Integrative Cancer Research at MIT
    Massachusetts General Hospital)

  • Sam Lauffer

    (Massachusetts General Hospital)

  • Wei Wei

    (Massachusetts General Hospital)

  • Qixian Chen

    (Koch Institute for Integrative Cancer Research at MIT)

  • Xiang Kang

    (Koch Institute for Integrative Cancer Research at MIT)

  • Haiqin Song

    (Koch Institute for Integrative Cancer Research at MIT)

  • Xi Yang

    (Koch Institute for Integrative Cancer Research at MIT)

  • Xing Huang

    (Koch Institute for Integrative Cancer Research at MIT)

  • Alexandre Detappe

    (Koch Institute for Integrative Cancer Research at MIT
    Dana Farber Cancer Institute
    Harvard Medical School)

  • Ursula Matulonis

    (Dana Farber Cancer Institute
    Harvard Medical School)

  • David Pepin

    (Massachusetts General Hospital
    Harvard Medical School)

  • Michael T. Hemann

    (Koch Institute for Integrative Cancer Research at MIT)

  • Michael J. Birrer

    (Massachusetts General Hospital
    Harvard Medical School)

  • P. Peter Ghoroghchian

    (Koch Institute for Integrative Cancer Research at MIT
    Dana Farber Cancer Institute
    Harvard Medical School)

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.

Suggested Citation

  • Ruogu Qi & Yongheng Wang & Peter M. Bruno & Haihua Xiao & Yingjie Yu & Ting Li & Sam Lauffer & Wei Wei & Qixian Chen & Xiang Kang & Haiqin Song & Xi Yang & Xing Huang & Alexandre Detappe & Ursula Matu, 2017. "Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02390-7
    DOI: 10.1038/s41467-017-02390-7
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