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Albumin/vaccine nanocomplexes that assemble in vivo for combination cancer immunotherapy

Author

Listed:
  • Guizhi Zhu

    (National Institutes of Health (NIH))

  • Geoffrey M. Lynn

    (NIH)

  • Orit Jacobson

    (National Institutes of Health (NIH))

  • Kai Chen

    (University of Southern California)

  • Yi Liu

    (National Institutes of Health (NIH)
    China Pharmaceutical University)

  • Huimin Zhang

    (National Institutes of Health (NIH))

  • Ying Ma

    (National Institutes of Health (NIH))

  • Fuwu Zhang

    (National Institutes of Health (NIH))

  • Rui Tian

    (National Institutes of Health (NIH))

  • Qianqian Ni

    (National Institutes of Health (NIH))

  • Siyuan Cheng

    (National Institutes of Health (NIH))

  • Zhantong Wang

    (National Institutes of Health (NIH)
    Xiamen University)

  • Nan Lu

    (National Institutes of Health (NIH))

  • Bryant C. Yung

    (National Institutes of Health (NIH))

  • Zhe Wang

    (National Institutes of Health (NIH))

  • Lixin Lang

    (National Institutes of Health (NIH))

  • Xiao Fu

    (NIH)

  • Albert Jin

    (NIH)

  • Ido D. Weiss

    (NIH)

  • Harshad Vishwasrao

    (National Institutes of Health)

  • Gang Niu

    (National Institutes of Health (NIH))

  • Hari Shroff

    (National Institutes of Health
    NIH)

  • Dennis M. Klinman

    (National Cancer Institute)

  • Robert A. Seder

    (NIH)

  • Xiaoyuan Chen

    (National Institutes of Health (NIH))

Abstract

Subunit vaccines have been investigated in over 1000 clinical trials of cancer immunotherapy, but have shown limited efficacy. Nanovaccines may improve efficacy but have rarely been clinically translated. By conjugating molecular vaccines with Evans blue (EB) into albumin-binding vaccines (AlbiVax), here we develop clinically promising albumin/AlbiVax nanocomplexes that self-assemble in vivo from AlbiVax and endogenous albumin for efficient vaccine delivery and potent cancer immunotherapy. PET pharmacoimaging, super-resolution microscopies, and flow cytometry reveal almost 100-fold more efficient co-delivery of CpG and antigens (Ags) to lymph nodes (LNs) by albumin/AlbiVax than benchmark incomplete Freund’s adjuvant (IFA). Albumin/AlbiVax elicits ~10 times more frequent peripheral antigen-specific CD8+ cytotoxic T lymphocytes with immune memory than IFA-emulsifying vaccines. Albumin/AlbiVax specifically inhibits progression of established primary or metastatic EG7.OVA, B16F10, and MC38 tumors; combination with anti-PD-1 and/or Abraxane further potentiates immunotherapy and eradicates most MC38 tumors. Albumin/AlbiVax nanocomplexes are thus a robust platform for combination cancer immunotherapy.

Suggested Citation

  • Guizhi Zhu & Geoffrey M. Lynn & Orit Jacobson & Kai Chen & Yi Liu & Huimin Zhang & Ying Ma & Fuwu Zhang & Rui Tian & Qianqian Ni & Siyuan Cheng & Zhantong Wang & Nan Lu & Bryant C. Yung & Zhe Wang & L, 2017. "Albumin/vaccine nanocomplexes that assemble in vivo for combination cancer immunotherapy," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02191-y
    DOI: 10.1038/s41467-017-02191-y
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