論文

国際誌
2017年11月8日

Matrix-binding checkpoint immunotherapies enhance antitumor efficacy and reduce adverse events.

Science translational medicine
  • Jun Ishihara
  • ,
  • Kazuto Fukunaga
  • ,
  • Ako Ishihara
  • ,
  • Hans M Larsson
  • ,
  • Lambert Potin
  • ,
  • Peyman Hosseinchi
  • ,
  • Gabriele Galliverti
  • ,
  • Melody A Swartz
  • ,
  • Jeffrey A Hubbell

9
415
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1126/scitranslmed.aan0401

Immune checkpoint blockade exhibits considerable antitumor activity, but previous studies have reported instances of severe treatment-related adverse events. We sought to explore local immune checkpoint blockade, with an antibody (Ab) form that would be retained intra- or peritumorally, limiting systemic exposure. To accomplish this, we conjugated the checkpoint blockade Abs to an extracellular matrix (ECM)-super-affinity peptide derived from placenta growth factor-2 (PlGF-2123-144). We show enhanced tissue retention and lower Ab concentrations in blood plasma after PlGF-2123-144 conjugation, reducing systemic side effects such as the risk of autoimmune diabetes. Peritumoral injections of PlGF-2123-144-anti-CTLA4 (cytotoxic T lymphocyte antigen 4) and PlGF-2123-144-anti-PD-L1 (programmed death ligand 1) Abs delayed tumor growth and prolonged survival compared to the unmodified Abs in genetically engineered murine tumor models of melanoma and breast cancer. The PlGF-2123-144-Abs increased tumor-infiltrating activated CD8+ and CD4+ T cells, resulting in a delay of distant tumor growth as well. This simple and translatable approach of engineered ECM-binding Abs may present a viable and safer approach in checkpoint blockade.

リンク情報
DOI
https://doi.org/10.1126/scitranslmed.aan0401
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29118259
ID情報
  • DOI : 10.1126/scitranslmed.aan0401
  • PubMed ID : 29118259

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