Protective and Therapeutic Effects of an IL-15:IL-15Rα-Secreting Cell-Based Cancer Vaccine Using a Baculovirus System

• Main Authors: Van Anh Do-Thi, Hayyoung Lee, Hye Jin Jeong, Jie-Oh Lee, Young Sang Kim
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Cancers
• Subjects: interleukin 15; interleukin 15Rα; B16F10 melanoma; CT-26; cytokine; anticancer
• Online Access: https://www.mdpi.com/2072-6694/13/16/4039

This study reports the use of the BacMam system to deliver and express self-assembling IL-15 and IL-15Rα genes to murine B16F10 melanoma and CT26 colon cancer cells. BacMam-based IL-15 and IL-15Rα were well-expressed and assembled to form the biologically functional IL-15:IL-15Rα complex. Immunization with this IL-15:IL-15Rα cancer vaccine delayed tumor growth in mice by inducing effector memory CD4⁺ and CD8⁺ cells and effector NK cells which are tumor-infiltrating. It caused strong antitumor immune responses of CD8⁺ effector cells in a tumor-antigen specific manner both in vitro and in vivo and significantly attenuated Treg cells which a control virus-infected cancer vaccine could induce. Post-treatment with this cancer vaccine after a live cancer cell injection also prominently delayed the growth of the tumor. Collectively, we demonstrate a vaccine platform consisting of BacMam virus-infected B16F10 or CT26 cancer cells that secrete IL-15:IL-15Rα. This study is the first demonstration of a functionally competent soluble IL-15:IL-15Rα complex-related cancer vaccine using a baculovirus system and advocates that the BacMam system can be used as a secure and rapid method of producing a protective and therapeutic cancer vaccine.