Combination of fucoidan-based magnetic nanoparticles and immunomodulators enhances tumour-localized immunotherapy

Chih Sheng Chiang, Yu Jung Lin, Rachel Lee, Yen Ho Lai, Hung Wei Cheng, Chia Hung Hsieh, Woei Cherng Shyu, San-Yuan Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Checkpoint immunotherapy that inhibits tumour immune evasion has demonstrated significant clinical success. However, the therapeutic response is limited to certain patient populations, and immunotoxicity as well as autoimmunity have compromised the therapeutic benefits. Here, we report on an inherently therapeutic fucoidan–dextran-based magnetic nanomedicine (IO@FuDex3) conjugated with a checkpoint inhibitor (anti-PD-L1) and T-cell activators (anti-CD3 and anti-CD28). IO@FuDex3 can repair the immunosuppressive tumour microenvironment by reinvigorating tumour-infiltrating lymphocytes, while targeting the nanomedicine via magnetic navigation to the tumour to minimize off-target effects. Treatment that combines IO@FuDex3 and magnetic navigation reduces the occurrence of adverse events and extends the median survival from 32 to 63 days with less than 1 per cent dose compared with soluble anti-PD-L1. Thus, we demonstrate the potential of integrating anti-PD-L1 and T-cell activators as a form of inherently therapeutic nanomedicine to augment the therapeutic index of combination checkpoint immunotherapy.

Original languageEnglish
Pages (from-to)746-754
Number of pages9
JournalNature nanotechnology
Volume13
Issue number8
DOIs
StatePublished - 1 Aug 2018

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