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


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-15R?, 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-15R? into CT26 colon cancer cells to target them for intracellular assembly. The secreted IL-15:IL-15R? complexes were confirmed in ELISA and Co-IP experiments. IL-15:IL15R? 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 cancercell vaccine using mitomycin C (MMC)-treated IL-15:IL15R? secreting CT26 clones. Three sets of experiments were evaluated; (1) therapeutics, (2) vaccination, and (3) longterm protection. Wild-type CT26-bearing mice treated with a single dose of MMC-inactivated secreted IL-15:IL-15R? clones prolonged survival compared to the control group. Survival of MMC-inactivated IL-15:IL-15R? 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-15R? 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-15R?, may offer the new tools for immunotherapy to treat cancer.

SUBMITTER: Thi VAD 

PROVIDER: S-EPMC6939657 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

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