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면역미생물공생연구단
면역 미생물 공생 연구단
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IL4 Receptor-Targeted Proapoptotic Peptide Blocks Tumor Growth and Metastasis by Enhancing Antitumor Immunity

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Title
IL4 Receptor-Targeted Proapoptotic Peptide Blocks Tumor Growth and Metastasis by Enhancing Antitumor Immunity
Author(s)
Vadevoo SMP; Jung-Eun Kim; Gunassekaran GR; Jung HK; Chi L; Kim DE; Lee SH; Sin-Hyeog Im; Lee B
Publication Date
2017-12
Journal
MOLECULAR CANCER THERAPEUTICS, v.16, no.12, pp.2803 - 2816
Publisher
AMER ASSOC CANCER RESEARCH
Abstract
Cellular cross-talk between tumors and M2-polarized tumorassociated 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 IL4Rexpressing 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 CD8þ 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 IL4Rexpressing cancers. Mol Cancer Ther; 16(12); 2803–16. (c) 2017 AACR(American Association for Cancer Research)
URI
https://pr.ibs.re.kr/handle/8788114/4146
ISSN
1535-7163
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
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