論文

国際誌
2020年5月

Collagen-binding IL-12 enhances tumour inflammation and drives the complete remission of established immunologically cold mouse tumours.

Nature biomedical engineering
  • Aslan Mansurov
  • Jun Ishihara
  • Peyman Hosseinchi
  • Lambert Potin
  • Tiffany M Marchell
  • Ako Ishihara
  • John-Michael Williford
  • Aaron T Alpar
  • Michal M Raczy
  • Laura T Gray
  • Melody A Swartz
  • Jeffrey A Hubbell
  • 全て表示

4
5
開始ページ
531
終了ページ
543
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41551-020-0549-2

Checkpoint-inhibitor (CPI) immunotherapy has achieved remarkable clinical success, yet its efficacy in 'immunologically cold' tumours has been modest. Interleukin-12 (IL-12) is a powerful cytokine that activates the innate and adaptive arms of the immune system; however, the administration of IL-12 has been associated with immune-related adverse events. Here we show that, after intravenous administration of a collagen-binding domain fused to IL-12 (CBD-IL-12) in mice bearing aggressive mouse tumours, CBD-IL-12 accumulates in the tumour stroma due to exposed collagen in the disordered tumour vasculature. In comparison with the administration of unmodified IL-12, CBD-IL-12 induced sustained intratumoural levels of interferon-γ, substantially reduced its systemic levels as well as organ damage and provided superior anticancer efficacy, eliciting complete regression of CPI-unresponsive breast tumours. Furthermore, CBD-IL-12 potently synergized with CPI to eradicate large established melanomas, induced antigen-specific immunological memory and controlled tumour growth in a genetically engineered mouse model of melanoma. CBD-IL-12 may potentiate CPI immunotherapy for immunologically cold tumours.

リンク情報
DOI
https://doi.org/10.1038/s41551-020-0549-2
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32284554
ID情報
  • DOI : 10.1038/s41551-020-0549-2
  • PubMed ID : 32284554

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