Associate Professor Ken Takahashi
As a clinician, I have been involved in the clinics of gastrointestinal malignancies. On the other hand, I have been engaged in basic research on innate immunity, which plays a critical role in both antitumoral and antiviral immunity. Through these experiences, I have been highly motivated to translate the ideas and results from basic research into clinical practice. In my laboratory, I will execute projects under the theme of the development of novel cancer immunotherapies enhancing the efficacy of PD-1 blockade by harnessing innate immunity.
Research and Education
Cancer immunity is initiated at the tumor site through innate immune activation and cancer antigen release. In situ vaccines, which stimulate innate immunity and promote cancer antigen release at the tumor site, induce cancer immunity mostly upstream. Therefore, they are expected to synergize with checkpoint inhibitors. These vaccines can (1) induce systemic, long-lasting memory responses with localized treatment, minimizing adverse effects, and (2) utilize patient-specific cancer antigens as vaccine antigens, enabling personalized vaccination without complex antigen isolation or identification required in neoantigen vaccine strategies. Advances in endoscopy, ultrasound, and intra-arterial catheterization have made therapeutic intervention feasible, supporting the clinical application of in situ vaccines. The primary goal of our laboratory is to develop in situ vaccines that maximize cancer immune activation through a two-pronged approach by injecting a unique innate immunity-activating adjuvant and enhancing tumor destruction to release patient’s own tumor antigens. This strategy, when applied in both therapeutic and neoadjuvant settings, is expected to synergize with PD-1 blockade, leading to the development of cutting-edge cancer immunotherapy.
Our goal is to develop next generation cancer immunotherapies that enhance the efficacy of PD-1 blockade. We will maximize immune activation at tumor sites using a two sided approach, i.e., unique innate immunity-activating adjuvant and enhanced tumor destruction.
Recet Publications
- Yaku, H., Takahashi, K., Okada, H., Kobiyama, K., Shiokawa, M., Uza, N., Kodama, Y., Ishii, K.J., Seno, H. Near-infrared photoimmunotherapy as a complementary modality to in situ vaccine in a preclinical pancreatic cancer model. Biochem. Biophys. Res. Commun. 737, 150534, 2024. DOI: https://www.sciencedirect.com/science/article/pii/S0006291X24010702?via%3Dihub
- Okada, H., Takahashi, K., Yaku, H., Kobiyama, K., Iwaisako, K., Zhao, X., Shiokawa, M., Uza, N., Kodama, Y., Ken J, Ishii., Seno, H. In situ vaccination using unique TLR9 ligand K3-SPG induces long-lasting systemic immune response and synergizes with systemic and local immunotherapy. Sci Rep 12, 2132 (2022). DOI: https://www.nature.com/articles/s41598-022-05702-0
- Wieland, SF., Takahashi, K., Boyd, B., Whitten-Bauer, C., Ngo, N., de la Torre, JC., Chisari, F.V.. Human plasmacytoid dendritic cells sense lymphocytic choriomeningitis virus-infected cells in vitro. J Virol. 88, 752-7, 2014. DOI: https://journals.asm.org/doi/10.1128/jvi.01714-13
- Takahashi, K., Asabe, S., Wieland, S., Garaigorta, U., Gastaminza, P., Isogawa, M., Chisari, F.V.. Plasmacytoid dendritic cells sense hepatitis C virus-infected cells, produce interferon, & inhibit infection. Proc Natl Acad Sci U S A 107, 7431-7436, 2010. DOI: https://www.pnas.org/doi/full/10.1073/pnas.1002301107
- Kawai, T., Takahashi, K., Sato, S., Coban, C., Kumar, H., Kato, H., Ishii, K.J., Takeuchi, O., Akira, S.. IPS-1, an adaptor triggering RIG-I- & Mda5-mediated type I interferon induction. Nat Immunol 6, 981-988, 2005. DOI: https://www.nature.com/articles/ni1243
Laboratory
Associate Professor：Ken Takahashi, M.D., Ph.D.