Cell-Based IL-15:IL-15Rα Secreting Vaccine as an Effective Therapy for CT26 Colon Cancer in Mice
Van Anh Do Thi1, Hyung Min Jeon1, Sang Min Park1, Hayyoung Lee2,*, and Young Sang Kim1,*
1Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 34134, Korea, 2Institute of Biotechnology, Chungnam National University, Daejeon 34134, Korea
Received August 22, 2019; Revised November 3, 2019; Accepted November 6, 2019.; Published online November 25, 2019.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

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-15Rα complex, immunotherapy, interleukin-15, interleukin 15 receptor alpha
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30 November 2019 Volume 42,
Number 11, pp. 739~819

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