IL4 Receptor-Targeted Proapoptotic Peptide Blocks Tumor Growth and Metastasis by Enhancing Antitumor Immunity
SCIE
SCOPUS
- Title
- IL4 Receptor-Targeted Proapoptotic Peptide Blocks Tumor Growth and Metastasis by Enhancing Antitumor Immunity
- Authors
- Vadevoo, Murugan Poongkavithai; Kim, Jung-Eun; Gunassekaran, Gowri Rangaswamy; Jung, Hyun-Kyung; Chi, Lianhua; Kim, Dong Eon; Lee, Seung-Hyo; Im, Sin-Hyeog; Lee, Byungheon
- Date Issued
- 2017-12
- Publisher
- AMER ASSOC CANCER RESEARCH
- Abstract
- 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 IL4-Rexpressing 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 IL4-Rexpressing cancers. (C) 2017 AACR.
- Keywords
- EPITHELIAL-MESENCHYMAL TRANSITION; BREAST-CANCER METASTASIS; INTERLEUKIN-4 RECEPTOR; CARCINOMA CELLS; HYBRID PEPTIDE; PHAGE DISPLAY; T-CELLS; MACROPHAGES; PROGRESSION; THERAPY
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/50466
- DOI
- 10.1158/1535-7163.MCT-17-0339
- ISSN
- 1535-7163
- Article Type
- Article
- Citation
- MOLECULAR CANCER THERAPEUTICS, vol. 16, no. 12, page. 2803 - 2816, 2017-12
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.