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

Molecules and Cells 2019년 42권 12호 p.869 ~ 883
 ( Thi Van Anh Do ) - Chungnam National University College of Natural Sciences Department of Biochemistry

 ( Jeon Hyung-Min ) - Chungnam National University College of Natural Sciences Department of Biochemistry
박상민 ( Park Sang-Min ) - Chungnam National University College of Natural Sciences Department of Biochemistry
이하영 ( Lee Hay-Young ) - Chungnam National University Institute of Biotechnology
김용상 ( Kim Young-Sang ) - Chungnam National University College of Natural Sciences Department of Biochemistry

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.

키워드

cell-based vaccine; CT26 colon carcinoma; IL-15:IL15Rα complex; immunotherapy; interleukin-15; interleukin 15 receptor alpha
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