論文

2017年4月12日

Vaccination targeting human HER3 alters the phenotype of infiltrating T cells and responses to immune checkpoint inhibition.

Oncoimmunology
  • Osada T
  • Morse MA
  • Hobeika A
  • Márcio Augusto Diniz
  • Gwin WR
  • Hartman Z
  • Wei J
  • Guo H
  • Yang XY
  • Liu CX
  • Kaneko K
  • Broadwater G
  • Herbert Kim Lyerly
  • 全て表示

記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.1080/2162402x.2017.1315495

Expression of human epidermal growth factor family member 3 (HER3), a critical heterodimerization partner with EGFR and HER2, promotes more aggressive biology in breast and other epithelial malignancies. As such, inhibiting HER3 could have broad applicability to the treatment of EGFR- and HER2-driven tumors. Although lack of a functional kinase domain limits the use of receptor tyrosine kinase inhibitors, HER3 contains antigenic targets for T cells and antibodies. Using novel human HER3 transgenic mouse models of breast cancer, we demonstrate that immunization with recombinant adenoviral vectors encoding full length human HER3 (Ad-HER3-FL) induces HER3-specific T cells and antibodies, alters the T cell infiltrate in tumors, and influences responses to immune checkpoint inhibitions. Both preventative and therapeutic Ad-HER3-FL immunization delayed tumor growth but were associated with both intratumoral PD-1 expressing CD8+ T cells and regulatory CD4+ T cell infiltrates. Immune checkpoint inhibition with either anti-PD-1 or anti-PD-L1 antibodies increased intratumoral CD8+ T cell infiltration and eliminated tumor following preventive vaccination with Ad-HER3-FL vaccine. The combination of dual PD-1/PD-L1 and CTLA4 blockade slowed the growth of tumor in response to Ad-HER3-FL in the therapeutic model. We conclude that HER3-targeting vaccines activate HER3-specific T cells and induce anti-HER3 specific antibodies, which alters the intratumoral T cell infiltrate and responses to immune checkpoint inhibition.

リンク情報
DOI
https://doi.org/10.1080/2162402x.2017.1315495
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28680745
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5486174
ID情報
  • DOI : 10.1080/2162402x.2017.1315495
  • ORCIDのPut Code : 136783521
  • PubMed ID : 28680745
  • PubMed Central 記事ID : PMC5486174

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