2019 Fiscal Year Annual Research Report
Analysis of B cell repertoires and their antigen specificity in peripheral blood from cancer patients undergoing anti-PD-1 antibody therapy.
| Project/Area Number |
18K19490
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| Research Institution | Kanagawa Cancer Center Research Institute |
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Principal Investigator |
笹田 哲朗 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), がんワクチン・免疫センター, 部長 (70293967)
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| Co-Investigator(Kenkyū-buntansha) |
紅露 拓 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), 臨床研究所, 技師・研究員 (90372424)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Keywords | 抗PD-1抗体 / B細胞 / B細胞受容体 / レパトア / 抗原 / バイオマーカー |
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| Outline of Annual Research Achievements |
本研究の目的は、抗PD-1抗体で治療された各種がんにおいて、① 末梢血のB細胞受容体（BCR）レパトア解析の臨床的意義（特に、治療効果・有害事象合併を予測するバイオマーカーとしての有用性）、② 有効例あるいは有害事象合併例において選択的に増殖するB細胞クローンの認識する抗原の同定と作用メカニズム（抗腫瘍効果、自己免疫反応）との関連、を明らかとすることである。本研究の成果は、抗PD-1抗体の作用メカニズムを解明するとともに、不必要な治療による不利益（有害事象合併・医療費浪費）の回避につながると期待される。
本年度には、① 抗PD-1抗体で治療された進行尿路上皮がん患者20例の治療開始前後に採取した末梢血単核球におけるBCR配列を決定し、前年度に測定した尿路上皮がん患者10例でのデータと合わせて統計学的に解析した。BCRレパトア多様性を治療前後で比較したところ、有害事象を合併した患者では治療後のBCRレパトア多様性が有意に減少した。ただし、治療後のBCRレパトア多様性の変化と治療効果との間には有意な相関を認めなかった。また、治療後のT細胞受容体（TCR）レパトア多様性の変化と治療効果・有害事象合併との間にも有意な相関を認めなかった。これまでの結果を総合すると、抗PD-1抗体治療後のBCRレパトア多様性の変化は進行非小細胞がん患者では治療効果と相関し、進行尿路上皮がん患者では有害事象合併と相関するものと示唆された。② BCR遺伝子解析の結果から、有害事象合併例の治療後に選択的に増加したB細胞クローンに由来するBCR（IgG H鎖およびL鎖）の遺伝子配列を同定し、精製抗体を作成した。現在、精製抗体の各種ヒト細胞株・組織に対する反応性を検討し、認識抗原を同定中である。
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[Journal Article] Identification of biomarkers for personalized peptide vaccination in 2,588 cancer patients.2020
Author(s)
Suekane S, Yutani S, Yamada A, Sasada T, Matsueda S, Takamori S, Toh U, Kawano K, Yoshiyama K, Sakamoto S, Sugawara S, Komatsu N, Yamada T, Naito M, Terasaki M, Mine T, Itoh K, Shichijo S, Noguchi M.
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Journal Title
Int J Oncol.
Volume: 56
Pages: 1479-1489
DOI
Peer Reviewed / Open Access
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[Journal Article] Distribution of Regulatory T-Cells and Other Phenotypes of T-Cells in Tumors and Regional Lymph Nodes of Colorectal Cancer Patients.2020
Author(s)
Kazama K, Otake J, Satoyoshi T, Shiozawa M, Sugano N, Sato S, Atsumi Y, Kano K, Murakawa M, Maezawa Y, Hashimoto I, Numata M, Oshima T, Yukawa N, Rino Y, Sasada T, Masuda M.
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Journal Title
In Vivo.
Volume: 34
Pages: 849-856
DOI
Peer Reviewed / Open Access
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[Journal Article] Mixed 20-peptide cancer vaccine in combination with docetaxel and dexamethasone for castration-resistant prostate cancer: a randomized phase II trial.2020
Author(s)
Noguchi M, Arai G, Egawa S, Ohyama C, Naito S, Matsumoto K, Uemura H, Nakagawa M, Nasu Y, Eto M, Suekane S, Sasada T, Shichijo S, Yamada A, Kakuma T, Itoh K.
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Journal Title
Cancer Immunol Immunother.
Volume: 69
Pages: 847-857
DOI
Peer Reviewed / Open Access
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[Journal Article] High expression of olfactomedin-4 is correlated with chemoresistance and poor prognosis in pancreatic cancer.2020
Author(s)
Ohkuma R, Yada E, Ishikawa S, Komura D, Ishizaki H, Tamada K, Kubota Y, Hamada K, Ishida H, Hirasawa Y, Ariizumi H, Satoh E, Shida M, Watanabe M, Onoue R, Ando K, Tsurutani J, Yoshimura K, Yokobori T, Sasada T, Aoki T, Murakami M, Norose T, Ohike N, Takimoto M, Izumizaki M, Kobayashi S, Tsunoda T, Wada S.
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Journal Title
PLoS One.
Volume: 15
Pages: e0226707
DOI
Peer Reviewed / Open Access
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[Journal Article] Heat shock protein 105 peptide vaccine could induce antitumor immune reactions in a phase I clinical trial.2019
Author(s)
Shimizu Y, Yoshikawa T, Kojima T, Shoda K, Nosaka K, Mizuno S, Wada S, Fujimoto Y, Sasada T, Kohashi K, Bando H, Endo I, Nakatsura T.
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Journal Title
Cancer Sci.
Volume: 110
Pages: 3049-3060
DOI
Peer Reviewed / Open Access
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[Presentation] High expression of Olfactomedin-4 correlates with chemoresistance and poor prognosis for pancreatic cancer.2019
Author(s)
Ryotaro Ohkuma, Erica Yada, Yutaro Kubota, Kazuyuki Hamada, Hiroo Ishida, Yuya Hirasawa, Hirotsugu Ariizumi, Etsuko Satoh, Junji Tsurutani, Kiyoshi Yoshimura, Tetsuro Sasada, Takeshi Aoki, Masahiko Murakami, Tomoko Norose, Nobuyuki Ohike, Masafumi Takimoto, Takuya Tsunoda, Satoshi Wada.
Organizer
AACR Annual Meeting 2019
Int'l Joint Research
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[Presentation] Early changes in plasma CXCL2 and MMP2 levels predicts the response to anti-PD-1 therapy in non-small-cell lung cancer.2019
Author(s)
Matsuo N, Azuma K, Murotani K, Ishii H, Tokito T, Yamada K,Shibata Y, Shimokawaji T, Nakahara Y, Kondo T, Kato T, Saito H, Yamada K, Sasada T, Hoshino T.
Organizer
2019 World Conference on Lung Cancer
Int'l Joint Research
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[Presentation] Proteogenomics-based identifying neoantigens in refractory cancers using xenograft mice.2019
Author(s)
Yuko Nakamura, Susumu Iizumi, Hiroki Ueda, Shogo Yamamoto, Kenji Tatsuno, Aya Nakayama, Kazuki Yamamoto, Taku Koro, Kyoko Hasegawa, Norihiro Nakamura, Hiroyuki Aburatani, Tetsuro Sasada, Takeshi Kawamura.
Organizer
18th Human Proteome Organization World Congress
Int'l Joint Research
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[Presentation] A novel affinity-enhanced NY-ESO-1-targeting TCR-redirected T cell transfer exhibited early-onset cytokine release syndrome and subsequent tumor responses in synovial sarcoma patients.2019
Author(s)
Hattori H, Ishihara M, Kitano S, Miyahara Y, Kato H, Mishima H, Yamamoto N, Funakoshi T, Kojima T, Sasada T, Sato E, Okamoto S, Tomura D, Chono H, Nukaya I, Mineno J, Ikeda H, Watanabe T, Kageyama S, Shiku H.
Organizer
ESMO 2019 Congress
Int'l Joint Research
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[Presentation] Tumor responses and early onset cytokine release syndrome in synovial sarcoma patients treated with a novel affinityenhanced NY-ESO-1-targeting TCR-redirected T cell transfer.2019
Author(s)
Ishihara M, Kitano S, Hattori H, Miyahara Y, Kato H, Mishima H, Yamamoto N, Funakoshi T, Kojima T, Sasada T, Sato E, Okamoto S, Tomura D, Chono H, Nukaya I, Mineno J, Ikeda H, Watanabe T, Kageyama S, Shiku H.
Organizer
ASCO Annual Meeting 2019
Int'l Joint Research
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[Presentation] Changes in plasma CXCL2 and MMP2 levels reflect response to anti-PD-1 therapy in non-small-cell lung cancer patients.2019
Author(s)
Norikazu Matsuo, Koichi Azuma, Kenta Murotani, Yoshiko Naito, Hidenobu Ishii, Takaaki Tokito, Tadasuke Shimokawaji, Yoshiro Nakahara, Tetsuro Kondo, Terufumi Kato Haruhiro Saito, Kouzo Yamada, Tetsuro Sasada, Tomoaki Hoshino.
Organizer
第17回日本臨床腫瘍学会学術集会
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[Presentation] Changes of BCR repertoire are predictive biomarker for the efficacy of immune checkpoint inhibitor in NSCLC.2019
Author(s)
Yoshiro Nakahara, Norikazu Matsuo, Koichi Azuma, Yoshiko Naito, Hidenobu Ishii, Takaaki Tokito, Yuka Igarashi, Taku Kouro, Ryo Usui, Tadasuke Shimokawaji, Tetsuro Kondo, Terufumi Kato, Haruhiro Saito, Kouzo Yamada, Tomoaki Hoshino, Tetsuro Sasada.
Organizer
第17回日本臨床腫瘍学会学術集会
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