IL4 Receptor-Targeted Proapoptotic Peptide Blocks Tumor Growth and Metastasis by Enhancing Antitumor Immunity.

Cellular cross-talk between tumors and M2-polarized tumor-associated macrophages (TAM) favors tumor progression. Upregulation of IL4 receptor (IL4R) is observed in diverse tumors and TAMs. We tested whether an IL4R-targeted proapoptotic peptide could inhibit tumor progression. The IL4R-binding peptide (IL4RPep-1) preferentially bound to IL4R-expressing tumor cells and M2-polarized macrophages both in vitro and in 4T1 breast tumors in vivo To selectively kill IL4R-expressing cells, we designed an IL4R-targeted proapoptotic peptide, IL4RPep-1-K, by adding the proapoptotic peptide (KLAKLAK)2 to the end of IL4RPep-1. IL4RPep-1-K exerted selective cytotoxicity against diverse IL4R-expressing tumor cells and M2-polarized macrophages. Systemic administration of IL4RPep-1-K inhibited tumor growth and metastasis in 4T1 breast tumor-bearing mice. Interestingly, IL4RPep-1-K treatment increased the number of activated cytotoxic CD8+ T cells while reducing the numbers of immunosuppressive regulatory T cells and M2-polarized TAMs. No significant systemic side effects were observed. These results suggest that IL4R-targeted proapoptotic peptide has potential for treating diverse IL4R-expressing cancers. Mol Cancer Ther; 16(12); 2803-16. ©2017 AACR.
AuthorsSri Murugan Poongkavithai Vadevoo, Jung-Eun Kim, Gowri Rangaswamy Gunassekaran, Hyun-Kyung Jung, Lianhua Chi, Dong Eon Kim, Seung-Hyo Lee, Sin-Hyeog Im, Byungheon Lee
JournalMolecular cancer therapeutics (Mol Cancer Ther) Vol. 16 Issue 12 Pg. 2803-2816 (Dec 2017) ISSN: 1538-8514 [Electronic] United States
PMID28878029 (Publication Type: Journal Article)
Copyright©2017 American Association for Cancer Research.
Chemical References
  • Peptides
  • Receptors, Interleukin-4
  • Animals
  • Apoptosis
  • Female
  • Humans
  • Mice
  • Neoplasm Metastasis
  • Peptides (metabolism)
  • Receptors, Interleukin-4 (metabolism)
  • Signal Transduction

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