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http://dx.doi.org/10.14348/molcells.2019.0188

Cell-Based IL-15:IL-15Rα Secreting Vaccine as an Effective Therapy for CT26 Colon Cancer in Mice  

Thi, Van Anh Do (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
Jeon, Hyung Min (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
Park, Sang Min (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
Lee, Hayyoung (Institute of Biotechnology, Chungnam National University)
Kim, Young Sang (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
Publication Information
Molecules and Cells / v.42, no.12, 2019 , pp. 869-883 More about this Journal
Abstract
Interleukin (IL)-15 is an essential immune-modulator with high potential for use in cancer treatment. Natural IL-15 has a low biological potency because of its short half-life and difficulties in mass-production. IL-15Rα, a member of the IL-15 receptor complex, is famous for its high affinity to IL-15 and its ability to lengthen the half-life of IL-15. We have double-transfected IL-15 and its truncated receptor IL-15Rα into CT26 colon cancer cells to target them for intracellular assembly. The secreted IL-15:IL-15Rα complexes were confirmed in ELISA and Co-IP experiments. IL-15:IL-15Rα secreting clones showed a higher anti-tumor effect than IL-15 secreting clones. Furthermore, we also evaluated the vaccine and therapeutic efficacy of the whole cancer-cell vaccine using mitomycin C (MMC)-treated IL-15:IL-15Rα secreting CT26 clones. Three sets of experiments were evaluated; (1) therapeutics, (2) vaccination, and (3) long-term protection. Wild-type CT26-bearing mice treated with a single dose of MMC-inactivated secreted IL-15:IL-15Rα clones prolonged survival compared to the control group. Survival of MMC-inactivated IL-15:IL-15Rα clone-vaccinated mice (without any further adjuvant) exceeded up to 100%. This protection effect even lasted for at least three months after the immunization. Secreted IL-15:IL-15Rα clones challenging trigger anti-tumor response via CD4+ T, CD8+ T, and natural killer (NK) cell-dependent cytotoxicity. Our result suggested that cell-based vaccine secreting IL-15:IL-15Rα, may offer the new tools for immunotherapy to treat cancer.
Keywords
cell-based vaccine; CT26 colon carcinoma; IL-15:$IL-15R{\alpha}$ complex; immunotherapy; interleukin-15; interleukin 15 receptor alpha;
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