Organization
School of Medicine Medical Course Basic Medicine Pathology[Immuno Pathology]
External link
KOSAKA Akemi
Degree
-
博士 (理学） ( 2007.3 北海道大学 )
Research Areas
-
Life Science / Immunology
Papers
-
Sato R., Inoue T., Wakisaka R., Komatsuda H., Kono M., Yamaki H., Ohara K., Kumai T., Kosaka A., Ohkuri T., Nagato T., Kishibe K., Kobayashi H., Takahara M.
Head & Neck 2025.3
-
Hypoxia-Targeted Immunotherapy with PD-1 Blockade in Head and Neck Cancer Reviewed
Wakisaka R, Yamaki H, Kono M, Inoue T, Sato R, Komatsuda H, Ohara K, Kosaka A, Ohkuri T, Nagato T, Kishibe K, Nakayama K, Kobayashi H, Kumai T, Takahara M.
Cancers 16 ( 17 ) 3013 - 3013 2024.8
-
Immunotherapy targeting tumor-associated antigen in a mouse model of head and neck cancer Reviewed
Kono M., Wakisaka R., Komatsuda H., Hayashi R., Kumai T., Yamaki H., Sato R., Nagato T., Ohkuri T., Kosaka A., Ohara K., Kishibe K., Kobayashi H., Hayashi T., Takahara M.
Head and Neck 46 ( 8 ) 2056 - 2067 2024.8
-
Murai A., Kubo T., Ohkuri T., Yanagawa J., Yajima Y., Kosaka A., Li D., Nagato T., Murata K., Kanaseki T., Tsukahara T., Nagasaki T., Hirohashi Y., Kobayashi H., Torigoe T.
Immunological Medicine 2024.6
-
Nagato T., Komatsuda H., Hayashi R., Takahara M., Ujiie N., Kosaka A., Ohkuri T., Oikawa K., Sato R., Wakisaka R., Kono M., Yamaki H., Ohara K., Kumai T., Kishibe K., Katada A., Hayashi T., Kobayashi H.
Cancer Science 2024.4
-
SARS-CoV-2 spike protein-derived immunogenic peptides that are promiscuously presented by several HLA-class II molecules and their potential for inducing acquired immunity Reviewed
Yajima Y., Kosaka A., Ohkuri T., Hirohashi Y., Li D., Nagasaki T., Nagato T., Torigoe T., Kobayashi H.
Heliyon 9 ( 9 ) e20192 2023.9
-
Brachyury-targeted immunotherapy combined with gemcitabine against head and neck cancer Reviewed
Yamaki H., Kono M., Wakisaka R., Komatsuda H., Kumai T., Hayashi R., Sato R., Nagato T., Ohkuri T., Kosaka A., Ohara K., Kishibe K., Takahara M., Hayashi T., Kobayashi H., Katada A.
Cancer Immunology, Immunotherapy 2023.8
-
Expression of soluble CD27 in extranodal natural killer/T-cell lymphoma, nasal type: potential as a biomarker for diagnosis and CD27/CD70-targeted therapy Reviewed
Nagato T., Komatsuda H., Hayashi R., Takahara M., Kishibe K., Yasuda S., Yajima Y., Kosaka A., Ohkuri T., Oikawa K., Harabuchi S., Kono M., Yamaki H., Wakisaka R., Hirata-Nozaki Y., Ohara K., Kumai T., Katada A., Hayashi T., Harabuchi Y., Kobayashi H.
Cancer Immunology, Immunotherapy 2023.7
-
Kosaka A., Yajima Y., Yasuda S., Komatsuda H., Nagato T., Oikawa K., Kobayashi H., Ohkuri T.
International Journal of Cancer 2023.4
-
Komatsuda H., Wakisaka R., Kono M., Kumai T., Hayashi R., Yamaki H., Sato R., Nagato T., Ohkuri T., Kosaka A., Ohara K., Takahara M., Katada A., Kobayashi H.
Cancer Science 2023.2
-
A tumor metastasis-associated molecule TWIST1 is a favorable target for cancer immunotherapy due to its immunogenicity Reviewed
Yajima Y., Kosaka A., Ishibashi K., Yasuda S., Komatsuda H., Nagato T., Oikawa K., Kitada M., Takekawa M., Kumai T., Ohara K., Ohkuri T., Kobayashi H.
Cancer Science 113 ( 8 ) 2526 - 2535 2022.8
-
Immunomodulation via FGFR inhibition augments FGFR1 targeting T-cell based antitumor immunotherapy for head and neck squamous cell carcinoma Reviewed
Kono M., Komatsuda H., Yamaki H., Kumai T., Hayashi R., Wakisaka R., Nagato T., Ohkuri T., Kosaka A., Ohara K., Kishibe K., Takahara M., Katada A., Hayashi T., Kobayashi H., Harabuchi Y.
Oncoimmunology 2022.1
-
Interruption of MDM2 signaling augments MDM2-targeted T cell-based antitumor immunotherapy through antigen-presenting machinery. Reviewed
Kono M., Kumai T., Hayashi R., Yamaki H., Komatsuda H., Wakisaka R., Nagato T., Ohkuri T., Kosaka A., Ohara K., Kishibe K., Takahara M., Katada A., Hayashi T., Celis E., Kobayashi H., Harabuchi Y.
Cancer Immunology, Immunotherapy 2021.12
-
CD47 blockade enhances the efficacy of intratumoral STING-targeting therapy by activating phagocytes. Reviewed
Kosaka A., Ishibashi K., Nagato T., Kitamura H., Fujiwara Y., Yasuda S., Nagata M., Harabuchi S., Hayashi R., Yajima Y., Ohara K., Kumai T., Aoki N., Komohara Y., Oikawa K., Harabuchi Y., Kitada M., Kobayashi H., Ohkuri T.
Journal of Experimental Medicine 218 ( 11 ) e20200792 2021.11
-
A critical role of STING-triggered tumor-migrating neutrophils for anti-tumor effect of intratumoral cGAMP treatment. Reviewed
Nagata M., Kosaka A., Yajima Y., Yasuda S., Ohara M., Ohara K., Harabuchi S., Hayashi R., Funakoshi H., Ueda J., Kumai T., Nagato T., Oikawa K., Harabuchi Y., Esteban C., Ohkuri T., Kobayashi H.
Cancer Immunology, Immunotherapy 70 ( 8 ) 2301 - 2312 2021.8
-
A stealth antigen SPESP1, which is epigenetically silenced in tumors, is a suitable target for cancer immunotherapy. Reviewed
Kosaka A., Yajima Y., Hatayama M., Ikuta K., Sasaki T., Hirai N., Yasuda S., Nagata M., Hayashi R., Harabuchi S., Ohara K., Ohara M., Kumai T., Ishibashi K., Hirata-Nozaki Y., Nagato T., Oikawa K., Harabuchi Y., Celis E., Okumura T., Ohsaki Y., Kobayashi H., Ohkuri T.
Cancer Science 112 ( 7 ) 2705 - 2713 2021.7
-
IFN-γ- and IL-17-producing CD8+ T (Tc17-1) cells in combination with poly-ICLC and peptide vaccine exhibit antiglioma activity. Reviewed
Ohkuri T., Kosaka A., Ikeura M., Salazar AM, Okada H.
Journal for ImmunoTherapy of Cancer 9 ( 6 ) e002426 2021.6
-
Expression of placenta-specific 1 and its potential for eliciting anti-tumor helper T-cell responses in head and neck squamous cell carcinoma Reviewed
Hayashi R., Nagato T., Kumai T., Ohara K., Ohara M., Ohkuri T., Hirata-Nozaki Y., Harabuchi S., Kosaka A., Nagata M., Yajima Y., Yasuda S., Oikawa K., Kono M., Kishibe K., Takahara M., Katada A., Hayashi T., Celis E., Harabuchi Y., Kobayashi H.
Oncoimmunology 10 ( 1 ) 1856545 2020.12
-
Phosphorylated vimentin as an immunotherapeutic target against metastatic colorectal cancer. Reviewed
Ohara M., Ohara K., Kumai T., Ohkuri T., Nagato T., Hirata-Nozaki Y., Kosaka A., Nagata M., Hayashi R., Harabuchi S., Yajima Y., Oikawa K., Harabuchi Y., Sumi Y., Furukawa H., Kobayashi H.
Cancer Immunology, Immunotherapy 2020.6
-
Intratumoral STING activations overcome negative impact of cisplatin on antitumor immunity by inflaming tumor microenvironment in squamous cell carcinoma Reviewed
Harabuchi S, Kosaka A, Yajima Y, Nagata M, Hayashi R, Kumai T, Ohara K, Nagato T, Oikawa K, Ohara M, Harabuchi Y, Ohkuri T, Kobayashi H.
Biochemical and Biophysical Research Communications 2020.2
-
PD-L1-specific helper T-cells exhibit effective antitumor responses: new strategy of cancer immunotherapy targeting PD-L1 in head and neck squamous cell carcinoma. Reviewed
Hirata-Nozaki Y, Ohkuri T, Ohara K, Kumai T, Nagata M, Harabuchi S, Kosaka A, Nagato T, Ishibashi K, Oikawa K, Aoki N, Ohara M, Harabuchi Y, Uno Y, Takei H, Celis E, Kobayashi H.
Journal of Translational Medicine 2019.6
-
Targeting phosphorylated p53 to elicit tumor-reactive T helper responses against head and neck squamous cell carcinoma Reviewed
Ohara K, Ohkuri T, Kumai T, Nagato T, Nozaki Y, Ishibashi K, Kosaka A, Nagata M, Harabuchi S, Ohara M, Oikawa K, Aoki N, Harabuchi Y, Celis E, Kobayashi H.
OncoImmunology 2018.8
-
Effects of STING stimulation on macrophages: STING agonists polarize into "classically" or "alternatively" activated macrophages? Reviewed
Ohkuri T., Kosaka A., Nagato T., Kobayashi H.
Human Vaccines & Immunotherapeutics 14 ( 2 ) 285 - 287 2018.2
-
Intratumoral injection of IFN-β induces chemokine production in melanoma and augments the therapeutic efficacy of anti-PD-L1 mAb. Reviewed
Uehara J., Ohkuri T., Kosaka A., Ishibashi K., Hirata Y., Ohara K., Nagato T., Oikawa K., Aoki N., Harabuchi Y., Ishida-Yamamoto A., Kobayashi H.
Biochemical and Biophysical Research Communications 490 ( 2 ) 521 - 527 2017.8
-
Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy. Reviewed
Nagato T., Ohkuri T., Ohara K., Hirata Y., Kishibe K., Komabayashi Y., Ueda S., Takahara M., Kumai T., Ishibashi K., Kosaka A., Aoki N., Oikawa K., Uno Y., Akiyama N., Sado M., Takei H., Celis E., Harabuchi Y., Kobayashi H.
Cancer Immunology, Immunotherapy 66 ( 7 ) 877 - 890 2017.7
-
Intratumoral administration of cGAMP transiently accumulates potent macrophages for anti-tumor immunity at a mouse tumor site. Reviewed
Ohkuri T., Kosaka A., Ishibashi K., Kumai T., Hirata Y., Ohara K., Nagato T., Oikawa K., Aoki N., Harabuchi Y., Celis E., Kobayashi H.
Cancer Immunology, Immunotherapy 66 ( 6 ) 705 - 716 2017.6
-
Epigenetic modification augments the immunogenicity of human leukocyte antigen G serving as a tumor antigen for T cell-based immunotherapy Reviewed
Ishibashi K., Ohkuri T., Kosaka A., Nagato T., Hirata Y., Ohara K., Oikawa K., Aoki N., Kobayashi H.
OncoImmunology 5 ( 6 ) e1169356 2016.3
-
Histamine deficiency promotes accumulation of immunosuppressive immature myeloid cells and growth of murine gliomas. Reviewed
Ahn B., Kohanbash G., Ohkuri T., Kosaka A., Chen X., Ikeura M., Wang TC, Okada H.
Oncoimmunology 4 ( 11 ) e1047581 2015.5
-
Transgene-derived overexpression of miR-17-92 in CD8(+) T-cells confers enhanced cytotoxic activity. Reviewed
Kosaka A., Ohkuri T., Ikeura M., Kohanbash G., Okada H.
Biochemical and Biophysical Research Communications 2015.3
-
Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma. Reviewed
Johnson LA, Scholler J., Ohkuri T., Kosaka A., Patel PR, McGettigan SE, Nace AK, Dentchev T., Thekkat P., Loew A., Boesteanu AC, Cogdill AP, Chen T., Fraietta JA, Kloss CC, Posey AD Jr, Engels B., Singh R., Ezell T., Idamakanti N., Ramones MH, Li N., Zhou L., Plesa G., Seykora JT, Okada H., June CH, Brogdon JL, Maus MV
Science Translational Medicine 2015.2
-
Protective role of STING against gliomagenesis: Rational use of STING agonist in anti-glioma immunotherapy Invited Reviewed
Ohkuri T., Ghosh A., Kosaka A., Sarkar SN, Okada H.
Oncoimmunology 4 ( 4 ) e999523 2015.1
-
STING Contributes to Antiglioma Immunity via Triggering Type I IFN Signals in the Tumor Microenvironment. Reviewed
Ohkuri T., Ghosh A., Kosaka A., Zhu J., Ikeura M., David M., Watkins SC, Sarkar SN, Okada H.
Cancer Immunology Research 2014.12
-
Pre-clinical validation of a humanized anti-EGFR variant III chimeric antigen receptor and phase I trial of CART-EGFRvIII in glioblastoma
Johnson LA, Scholler J., Ohkuri T., Kosaka A., Patel PR, McGettigan SE, Nace A., Thekkat P., Loew A., Chen TJ, Fraietta JA, Posey AD, Boesteanu AC, Cogdill AP, Engels B., Singh R., Ezell TR, Idamakanti N., Plesa G., Seykora J., Okada H., June C., Brogdon J., Maus M.
Journal for ImmunoTherapy of Cancer 2 ( Suppl 3 ) O1 - O1 2014.11
-
Combination of an agonistic anti-CD40 monoclonal antibody and the COX-2 inhibitor celecoxib induces anti-glioma effects by promotion of type-1 immunity in myeloid cells and T-cells. Reviewed
Kosaka A., Ohkuri T., Okada H.
Cancer Immunology, Immunotherapy 63 ( 8 ) 847 - 857 2014.8
-
Activated hepatic stellate cells are dependent on self-collagen, cleaved by membrane type 1 matrix metalloproteinase for their growth. Reviewed
Birukawa NK, Murase K., Sato Y., Kosaka A., Yoneda A., Nishita H., Fujita R., Nishimura M., Ninomiya T., Kajiwara K., Miyazaki M., Nakashima Y., Ota S., Murakami Y., Tanaka Y., Minomi K., Tamura Y., Niitsu Y.
The Journal of Biological Chemistry 289 ( 29 ) 20209 - 20221 2014.7
-
Expression of miR-17-92 enhances anti-tumor activity of T-cells transduced with the anti-EGFRvIII chimeric antigen receptor in mice bearing human GBM xenografts. Reviewed
Ohno M., Ohkuri T., Kosaka A., Tanahashi K., June CH, Natsume A., Okada H.
Journal for ImmunoTherapy of Cancer 2013.12
-
Premetastatic soil and prevention of breast cancer brain metastasis. Reviewed
Liu Y., Kosaka A., Ikeura M., Kohanbash G., Fellows-Mayle W., Snyder LA, Okada H.
Neuro-Oncology 15 ( 7 ) 891 - 903 2013.7
-
Double-stranded RNA of intestinal commensal but not pathogenic bacteria triggers production of protective interferon-β. Reviewed
Kawashima T., Kosaka A., Yan H., Guo Z., Uchiyama R., Fukui R., Kaneko D., Kumagai Y., You DJ, Carreras J., Uematsu S., Jang MH, Takeuchi O., Kaisho T., Akira S., Miyake K., Tsutsui H., Saito T., Nishimura I., Tsuji NM
Immunity 38 ( 6 ) 1187 - 1197 2013.6
-
Lactococcus lactis subsp. cremoris FC triggers IFN-γ production from NK and T cells via IL-12 and IL-18. Reviewed
Kosaka A., Yan H., Ohashi S., Gotoh Y., Sato A., Tsutsui H., Kaisho T., Toda T., Tsuji NM
International Immunopharmacology 14 ( 4 ) 729 - 733 2012.12
-
Lactobacillus plantarum strain YU from fermented foods activates Th1 and protective immune responses. Reviewed
Kawashima T., Hayashi K., Kosaka A., Kawashima M., Igarashi T., Tsutsui H., Tsuji NM, Nishimura I., Hayashi T., Obata A.
International Immunopharmacology 2011.12
-
Extraction and purification of human interleukin-10 from transgenic rice seeds. Reviewed
Fujiwara Y., Aiki Y., Yang L., Takaiwa F., Kosaka A., Tsuji NM, Shiraki K., Sekikawa K.
Protein Expression and Purification 2010.7
-
Oral tolerance: intestinal homeostasis and antigen-specific regulatory T cells Invited Reviewed
Tsuji NM, Kosaka A.
Trends in Immunology 29 ( 11 ) 532 - 540 2008.11
-
AsialoGM1+CD8+ central memory-type T cells in unimmunized mice as novel immunomodulator of IFN-gamma-dependent type 1 immunity. Reviewed
Kosaka A., Wakita D., Matsubara N., Togashi Y., Nishimura S., Kitamura H., Nishimura T.
International Immunology 2007.3
-
Interleukin-12-responding asialoGM1+CD8+ central memory-type T cells as precursor cells for interferon-gamma-producing killer T cells. Reviewed
Kosaka A., Lee U., Wakita D., Matsubara N., Togashi Y., Nishimura S., Kitamura H., Nishimura T.
Cancer Science 2006.11
MISC
-
CD47遮断は，食細胞を活性化することにより，腫瘍内STINGターゲッティング療法の有効性を高める
大栗敬幸, 小坂朱, 小林博也
臨床免疫・アレルギー科 78 ( 6 ) 723 - 728 2022.12
-
がんの免疫逃避を打破する治療法の開発
大栗敬幸, 小坂朱, 小林博也
バイオサイエンスとインダストリー 80 ( 4 ) 330 - 332 2022.7
-
STINGリガンドと抗CD47抗体の併用によるがん免疫療法
大栗敬幸, 小坂朱, 小林博也
医学のあゆみ 2022.5
-
新たながん抗原同定技術に基づく治療戦略 1）DNAメチル化によるがん抗原発現の制御
大栗敬幸, 小坂朱, 小林博也
腫瘍内科 27 ( 5 ) 552 - 557 2021.5
-
ステルスがん抗原
大栗敬幸, 小坂朱, 小林博也
臨床免疫・アレルギー科 75 ( 5 ) 539 - 543 2021.5
Presentations
-
Effects of tumor-derived IL-6 on the tumor microenvironment and anti-tumor immune responses
Akemi Kosaka, Takayuki Ohkuri, Nanami Ujiie, Toshihiro Nagato, Hiroya Kobayashi
第83回 日本癌学会学術総会
-
Development of a combination therapy of STING agonist and IL-6 receptor inhibitor for TNBC
Akemi Kosaka, Takayuki Ohkuri, Hiroki Komatsuda, Nanami Ujiie, Toshihiro Nagato, Hiroya Kobayashi
第113回日本病理学会総会
-
Characterization of moDCs in the tumor-draining LNs by intratumoral colchicine-induced tumor vascular disruption
Akemi Kosaka, Shunsuke Yasuda, Takayuki Ohkuri, Hiroki Komatsuda, Toshihiro Nagato, Kensuke Oikawa, Hiroya Kobayashi
第82回 日本癌学会学術総会
-
Comparison of type I IFN-induced agonists in the tumor microenvironment
Akemi Kosaka, Takayuki Ohkuri, Shunsuke Yasuda, Hiroki Komatsuda, Toshihiro Nagato, Kensuke Oikawa, Hiroya Kobayashi
第112回 日本病理学会総会
-
Investigation of the ability of inducing type I IFNs in the tumor microenvironment
Akemi Kosaka, Takayuki Ohkuri, Yuki Yajima, Shunsuke Yasuda, Hiroki Komatsuda, Toshihiro Nagato, Kensuke Oikawa, Hiroya Kobayashi
第81回 日本癌学会学術総会
-
CD47 expression is associated with the infiltrations of CD8 and CD68 cells in breast cancer tissues
Akemi Kosaka, Takayuki Ohkuri, Yuki Yajima, Shunsuke Yasuda, Hiroki Komatsuda, Marino Nagata, Toshihiro Nagato, Kensuke Oikawa, Hiroya Kobayashi
第111回 日本病理学会総会
-
Combined treatment with celecoxib improves antitumor efficacy of STING agonists
Akemi Kosaka, Takayuki Ohkuri, Yuki Yajima, Shunsuke Yasuda, Hiroki Komastuda, Marino Nagata, Toshihiro Nagato, Kensuke Oikawa, Hiroya Kobayashi
第80回 日本癌学会学術総会
-
Epigenetically silenced antigens in tumor cells would be suitable targets for cancer immunotherapy
Akemi Kosaka, Takayuki Ohkuri, Yuki Yajima, Shunsuke Yasuda, Marino Nagata, Toshihiro Nagato, Kensuke Oikawa, Hiroya Kobayashi
第110回 日本病理学会総会
-
A role of IRF3 in antitumor immune response
Akemi Kosaka, Takayuki Ohkuri, Marino Nagata, Shohei Harabuchi, Ryusuke Hayashi, Yuki Yajima, Toshihiro Nagato, Kensuke Oikawa, Hiroya Kobayashi
第109回 日本病理学会総会
Industrial property rights
-
がん抗原ペプチド
大栗敬幸, 小坂朱, 小林博也
-
がん抗原ペプチド
大栗敬幸, 小坂朱, 小林博也
Research Projects
-
がん免疫治療の奏効率向上を目指した腫瘍微小環境内の良質な炎症状態の誘導戦略
2023.4 - 2026.3
基盤研究(B)
大栗 敬幸, 小坂 朱, 長門 利純, 小林 博也
がん免疫治療の成否はがん特異的T細胞の誘導能に依存するが、がん患者ではその誘導能が低い場合が多い。これまでに抗原提示細胞の貪食促進によるがん所属リンパ節(TDLN)内のがん特異的T細胞の分裂が増強されることや、腫瘍組織内で誘導される炎症状態の質によりTDLN内の単球由来樹状細胞(moDC)の質や量に差異が生じることを示した。そこで、TDLN内のmoDCは腫瘍内における炎症状態の質を反映すると同時にがん特異的T細胞の誘導に関わると考え、本研究では、moDCの教育力を向上させる腫瘍組織の炎症状態を解明するとともに、「TDLN内のmoDC」と「がん免疫治療の効果や生命予後」との関連を評価する。
-
cGAS/STING/I型IFN経路を基軸とした癌免疫微小環境のホット化治療戦略
Grant number：22H02838 2022.4 - 2025.3
日本学術振興会 科学研究費助成事業 基盤研究(B)
小林 博也, 大栗 敬幸, 長門 利純, 小坂 朱
Grant amount：\17,420,000 （ Direct Cost: \13,400,000 、 Indirect Cost：\4,020,000 ）
-
STINGアゴニストを用いたTNBCに対する効果的ながん免疫療法の開発
Grant number：22K06955 2022.4 - 2025.3
日本学術振興会 科学研究費助成事業 基盤研究(C)
小坂 朱
Grant amount：\4,160,000 （ Direct Cost: \3,200,000 、 Indirect Cost：\960,000 ）
-
Induction of type I IFN in the immunosuppressive tumor microenvironment
Grant number：18K07009 2018.4 - 2021.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Kosaka Akemi
Grant amount：\4,550,000 （ Direct Cost: \3,500,000 、 Indirect Cost：\1,050,000 ）
We performed real-time PCR and RNA sequencing analysis of tumor-associated macrophages derived from mouse tumor tissues. It was found that STING agonist induced higher levels of type I IFN compared with TLR agonists and TLR3 agonist induced lower levels of genes associated with DNA sensors and TLR-signaling pathways. In using mouse born-marrow derived immunosuppressive macrophages, agonists of not only TLR3 but also TLR4, TLR7 and TLR9 showed decreased type I IFN expression. Furthermore, it was suggested that IL-13 signaling may contribute to decreased induction of type I IFN expression by TLR agonists in the immunosuppressive microenvironment.
-
新規ステルス癌抗原を標的とした臨床応用可能な癌ワクチン製剤の開発
2016.5 - 2019.5
大塚製薬株式会社
-
Analysis of stealth antigens for developing tumor immunotherapy
Grant number：16K15244 2016.4 - 2018.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
Kobayashi Hiroya
Grant amount：\3,640,000 （ Direct Cost: \2,800,000 、 Indirect Cost：\840,000 ）
We found several stealth antigens which are epigenetically suppressed in tumor cells due to their high antigenicity and re-transcripted and -translated by treating with DNA methyltransferase inhibitor. We found that the stealth antigen-specific Th cells were efficiently generated from peripheral blood mononuclear cells from healthy donors. Also combination therapy of the Th cells and DNA methyltransferase inhibitor efficiently inhibited growth of human cancer cell line in immunodeficient mice.
-
Cancer immunotherapy by combining the selective COX-2 inhibitor and type I IFN signaling
Grant number：16K19071 2016.4 - 2018.3
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
KOSAKA Akemi
Grant amount：\3,900,000 （ Direct Cost: \3,000,000 、 Indirect Cost：\900,000 ）
The aim for this study is to development of an efficient and convenient cancer immunotherapy and to elucidate the mechanism when combining the selective COX-2 inhibitor celecoxib and the type I IFN inducer 2’3’-cGAMP.We used different mouse tumor models to determine the treatment regimen of celecoxib and 2’3’-cGAMP. The combination therapy showed a significant antitumor effect on tumor growth in mice compared to control and monotherapy with celecoxib or 2’3’-cGAMP. The antitumor effect of the combination therapy was not dependent on CD8+ T-cells and macrophages, and it was suggested that the type I IFN signaling pathway may not be involved in the antitumor responses of the combination therapy.
-
メチル化制御を受ける癌抗原分子を標的とした癌ワクチン製剤の開発
2016.4 - 2017.3
その他省庁等
癌細胞においてメチル化制御によって発現が抑制されている癌抗原分子におけるT細胞活性化領域を同定し、がんワクチン製剤を開発する。
-
STINGアゴニストによる抗腫瘍効果をより高める免疫抑制細胞の制御方法の開発
2015.10 - 2016.9
旭川医科大学
近年、小胞体に局在するSTING (stimulator of interferon genes) が、細胞質のDNAセンサータンパク質としての機能を持ち、type I interferon (IFN) シグナルを介したウイルスおよび細菌感染に対する自然免疫応答の誘導に重要であることが明らかになった。また、type I IFNは抗腫瘍免疫にも関与しており、type I IFNシグナルの欠損によりメラノーマや悪性軟部腫瘍など多様な種類のがんで腫瘍の形成が促進されることが報告されている。一方、がん微小環境では免疫抑制細胞が誘導され、抗腫瘍免疫応答の回避となる一因になっており、免疫抑制細胞の存在率と、がんの進行度や予後に相関関係があることが報告されている。申請者らは以前に、がんモデルマウスを用いた実験において、１）STINGアゴニストの投与により抗腫瘍免疫が誘導されること、２）がん微小環境における免疫抑制細胞の集積を抑制することにより転移を抑制すること、３）免疫抑制細胞の制御と同時に、免疫反応を活性化させる各々２つのシグナルが効果的な抗腫瘍免疫の誘導に重要であることを見出した。そこで本研究において、STINGアゴニストと免疫抑制細胞の制御を組み合わせたより効果的な抗腫瘍免疫を誘導する方法を開発するために、STINGアゴニストによる抗腫瘍効果をより高める免疫抑制細胞の制御方法を見出すことを目的とする。
-
がん免疫療法の開発
科学研究費補助金