Enhanced Anti-Tumor (Anti-Proliferation) Activity of Recombinant Human Interleukin-29 (IL-29) Mutants Using Site-Directed Mutagenesis Method.
Interferon (IFN)-λ, also known as IL-28A, IL-28B, or IL-29, is a new type III IFN, which shares many functional characteristics with type I IFN (α/β). Currently, IFN-α is used in the treatment of certain forms of cancer with severe adverse effects. Some researches had stated that IFN-λs induced a similar but restricted growth inhibition of tumor cells relative to IFN-α; moreover, mutations of IFN-λs could strongly impact its biological properties. In this study, three hIL-29 mutants (K33R, R35K, and K33R/R35K) were generated by site-directed mutagenesis and efficiently expressed in Pichia pastoris GS115, which have considerable abilities to inhibit the growth of BEL-7402, HCT-8, and SGC-7901 tumor cells in vitro. The results showed that these mutants (K33R, R35K, and K33R/R35K) exhibited a significantly enhanced anti-proliferation activity against these tumor cells, compared with native hIL-29 in vitro. Further assay in vitro indicated that superior to K33R and R35K, K33R/R35K had a significant increase in anti-tumor activity compared with IFN-α2b, which suggested that the K33R/R35K could make improvement for the effectiveness of native hIL-29 in clinic and could be used as a potentially powerful candidate for cancer immunotherapy.
School of Pharmaceutical Sciences, Jiangnan University, No. 1800 Lihu Road, Wuxi, 214122, China. moki365@163.com.
Yuan
Y
Lu
School of Biotechnology, Jiangnan University, No. 1800 Lihu Road, Wuxi, 214122, China. liliyun1219@163.com.
Liyun
L
Li
Wuxi Medical School, Jiangnan University, No. 1800 Lihu Road, Wuxi, 214122, China. chenwei@jiangnan.edu.cn.
Wei
W
Chen
Wuxi Medical School, Jiangnan University, No. 1800 Lihu Road, Wuxi, 214122, China. biowmc@126.com.
Minchen
M
Wu
D019943:Amino Acid Substitution; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics / Q000494:pharmacology*; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000095022:Interferon Lambda
D000970:Antineoplastic Agents; D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
Anti-proliferation activity; Human interleukin-29; Interferon-α; Site-directed mutagenesis; Tumor cell