Center for Cancer Immunotherapy and Immunobiology

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Division of Clinical Pharmacology and Cancer Immunotherapy
We are at the forefront of pioneering research and development in new molecular targeted therapies and immunotherapies that focus on the vulnerabilities arising from genetic alterations in cancer cells (such as KRAS, TP53, etc.). Our mission is to develop effective and safe treatments tailored to individual patients, with the aim of curing intractable cancers, such as unresectable gastrointestinal cancers.

Research Focus

The genetic changes that drive cellular carcinogenesis are diverse and complex. However, recent advances in comprehensive genetic analysis have shed light on their frequency, mechanisms of action, and significance. Our laboratory is dedicated to developing treatments that have a significant impact on cancer cells with minimizing effects on normal cells. We focus on developing therapies that specifically target genetic alterations found in cancer cells. In particular, we investigate the functions of “oncogenes” such as KRAS and “tumor suppressor genes” like TP53, exploring and validating the efficacy and safety of inhibitors targeting proteins associated with these genes. We conduct our research by using cancer and normal cells derived from humans and mice, combined with various gene editing and screening technologies.

Members

Professors

Associate Professor
Osamu Kikuchi

Goals

Selected Publications

Nguyen Vu TH, Kikuchi O, Ohashi S, Saito T, Ida T, Nakai Y, Cao Y, Yamamoto Y, Kondo Y, Mitani Y, Kataoka S, Kondo T, Katada C, Yamada A, Matsubara J, Muto M. Combination therapy with WEE1 inhibition and trifluridine/tipiracil against esophageal squamous cell carcinoma. Cancer Sci. 2023 Dec;114(12):4664-4676. https://doi.org/10.1111/cas.15966. Epub 2023 Sep 19. PMID: 37724648; PMCID: PMC10728021.

Jo, N., Hidaka, Y., Kikuchi, O., Fukahori, M., Sawada, T., Aoki, M., Yamamoto, M., Nagao, M., Morita, S., Nakajima, T., Muto, M., & Hamazaki, Y. (2023). Impaired CD4+ T cell response in older adults is associated with reduced immunogenicity and reactogenicity of mRNA COVID-19 vaccination. Nature Aging, 3(1), 82-92. https://doi.org/10.1038/s43587-022-00343-4

Li, T., Kikuchi, O., Zhou, J., Wang, Y., Pokharel, B., Bastl, K., Gokhale, P., Knott, A., Zhang, Y., Doench, J. G., Ho, Z. V., Catenacci, D. V., & Bass, A. J. (2023). Developing SHP2-based combination therapy for KRAS-amplified cancer. JCI Insight, 8(3), e152714. https://doi.org/10.1172/jci.insight.152714

Abe, T., Horisawa, Y., Kikuchi, O., Ozawa-Umeta, H., Kishimoto, A., Katsuura, Y., Imaizumi, A., Hashimoto, T., Shirakawa, K., Takaori-Kondo, A., Yusa, K., Asakura, T., Kakeya, H., & Kanai, M. (2022). Pharmacologic characterization of TBP1901, a prodrug form of aglycone curcumin, and CRISPR-Cas9 screen for therapeutic targets of aglycone curcumin. Eur J Pharmacol, 935, 175321. https://doi.org/10.1016/j.ejphar.2022.175321

Mitani, Y., Ohashi, S., Kikuchi, O., Nakai, Y., Ida, T., Mizumoto, A., Yamamoto, Y., Saito, T., Kataoka, S., Matsubara, J., Yamada, A., Kanai, M., Matsumoto, S., Sakai, H., Yoshikawa, K., Nakamura, E., & Muto, M. (2022). HER2 G776S mutation promotes oncogenic potential in colorectal cancer cells when accompanied by loss of APC function. Sci Rep, 12(1), 9213. https://doi.org/10.1038/s41598-022-13189-y

Mori, Y., Kikuchi, O., Horimatsu, T., Hara, H., Hironaka, S., Kojima, T., Kato, K., Tsushima, T., Ishihara, R., Mukai, K., Uozumi, R., Tada, H., Kasai, H., Kawaguchi, A., & Muto, M. (2022). Multicenter phase II study of trifluridine/tipiracil for esophageal squamous carcinoma refractory/intolerant to 5-fluorouracil, platinum compounds, and taxanes: the ECTAS study. Esophagus, 19(3), 444-451. https://doi.org/10.1007/s10388-021-00905-2

Ohashi, S., Maruno, T., Fukuyama, K., Kikuchi, O., Sunami, T., Kondo, Y., Imai, S., Matsushima, A., Suzuki, K., Usui, F., Yakami, M., Yamada, A., Isoda, H., Matsumoto, S., Seno, H., Muto, M., & Inoue, M. (2021). Visceral fat obesity is the key risk factor for the development of reflux erosive esophagitis in 40-69-years subjects. Esophagus, 18(4), 889-899. https://doi.org/10.1007/s10388-021-00859-5

Ohashi, S., Kikuchi, O., Nakai, Y., Ida, T., Saito, T., Kondo, Y., Yamamoto, Y., Mitani, Y., Nguyen Vu, T. H., Fukuyama, K., Tsukihara, H., Suzuki, N., & Muto, M. (2020). Synthetic Lethality with Trifluridine/Tipiracil and Checkpoint Kinase 1 Inhibitor for Esophageal Squamous Cell Carcinoma. Mol Cancer Ther, 19(6), 1363-1372. https://doi.org/10.1158/1535-7163.MCT-19-0918

Sethi, N. S., Kikuchi, O., Duronio, G. N., Stachler, M. D., McFarland, J. M., Ferrer-Luna, R., Zhang, Y., Bao, C., Bronson, R., Patil, D., Sanchez-Vega, F., Liu, J. B., Sicinska, E., Lazaro, J. B., Ligon, K. L., Beroukhim, R., & Bass, A. J. (2020). Early TP53 alterations engage environmental exposures to promote gastric premalignancy in an integrative mouse model. Nat Genet, 52(2), 219-230. https://doi.org/10.1038/s41588-019-0574-9

Nagaraja, A. K., Kikuchi, O., & Bass, A. J. (2019). Genomics and Targeted Therapies in Gastroesophageal Adenocarcinoma. Cancer Discov, 9(12), 1656-1672. https://doi.org/10.1158/2159-8290.Cd-19-0487

Recruitment & Contact

Currently, we are looking for a technician. You can find further information here.

Moreover, we are permanently recruiting highly motivated students and postdoctoral fellows, regardless of previous scientific backgrounds.

Please contact us using CCII’s contact form or by directly sending an email to recruit_ccii@mail2.adm.kyoto-u.ac.jp. Please indicate in which position and subject area you are interested in and that your inquiry is about our research division.

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