Melittin-MIL-2 fusion protein as a candidate for cancer immunotherapy

• DOI: 10.1186/s12967-016-0910-0
• Publication Date: 2016-05-31T23:39:28Z
• Authors: Mingjun Liu; Haitao Wang; Linjie Liu; Bin Wang; Guirong Sun
• Keywords: Melittin; Cancer Immunotherapy

Cytokine fusion protein that modulates the immune response holds great potential for cancer immunotherapy. IL-2 is an effective treatment against advanced cancers. However, therapeutic efficacy of limited by severe systemic toxicity. Several mutants recombinant can increase antitumor activity and minimize Melittin attractive anticancer candidate because its wide-spectrum lytic properties. We previously generated a bifunctional melittin-MIL-2, composed melittin mutant IL-2. The melittin-MIL-2 inhibited growth human ovarian SKOV3 cells in vitro vivo tumor growth. whether this effect could also be used immunotherapy was unknown. To assess potential, we further investigated more cancers different tissue origins vivo.The specific tested on cytokine dependent cell line CTLL-2. cytolytic detected standard 4-h (51)Cr-release assays. PBMC stimulation to determined IFN-γ release assay. observed proliferation MTT ability inhibit evaluated using liver (SMMC-7721 cells), lung (A549 cells) (SKOV3 xenograft models. immunity within microenvironment, level some cytokines including IFN-γ, TNF-α, IL-12 IL-4 analyzed ELISA. injected MDA-MB-231 into mice, anti-metastatic examined counting nodules lung.The inducing T NK-cell cytotoxicity. significantly increased production PBMCs. In vitro, mediated killing or directly killed lines origins. vivo, exhibited stronger inhibition transplanted tumors compared rIL-2. promoted secretion tissues decreased immunosuppressive vivo. Furthermore, reduced metastasis breast cancer.This study provides evidence produce effects, potent