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再生医療（AMED）
分担研究者：東北大学 加藤幸成（代表：京都大学 金子 新）
令和５年度〜令和７年度
課題名：GPC3 CAR 発現 iPS 細胞由来 ILC/NK 細胞の患者体内生存延長 と抗腫瘍
エフェクター機能向上を目指したリバーストランスレーショナル研究
東北大学ではこれまで、がん細胞に特異的な反応性を示すモノクローナル抗体の作製法（CasMab法）を用いることにより、ポドプラニンに対して、複数のCasMabの作製に成功した。ポドプラニンはリンパ管内皮細胞、肺胞上皮細胞、皮膚基底細胞、腎上皮細胞などの全身の正常細胞に高発現し、通常の抗体では様々な副作用が懸念される。CasMabはそれらの正常細胞に反応せず、肺がん、食道がん、悪性中皮腫、悪性脳腫瘍、卵巣がんなどの複数の難治性がんに高い反応性を示すため、抗体医薬の新規ターゲットとして期待される。さらに、乳がんや膵がんの他に血管内皮細胞などの正常細胞にも高発現しているポドカリキシンに対しても、がん特異的な反応性を示すCasMabを複数作製してきた。本プロジェクトにおいては、京都大学が保有するがん特異的抗体をヒト化あるいはscFv化し、CAR-Tに搭載できるフォーマットへの最適化を行う。
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＜文献＞
23bm1123027h0001
2024
20. Arimori T, Mihara E, Suzuki H, Ohishi T, Tanaka T, Kaneko MK, Takagi J, Kato Y.
Locally misfolded HER2 expressed on cancer cells is a promising target for development of cancer-specific antibodies
Structure, 32(5),536-549, https://doi.org/10.1016/j.str.2024.02.007, 2024 (PDF)
19. Li G, Tanaka T, Suzuki H, Kaneko MK, Kato Y.
Cx1Mab-1: A Novel Anti-mouse CXCR1 Monoclonal Antibody for Flow Cytometry
Monoclon. Antib. Immunodiagn. Immunother.,43(2), 59-66, DOI: 10.20944/preprints202311.0501.v2, 2023 (PDF;preprint)
18. Ouchida T, Li G, Suzuki H, Yanaka M, Nakamura T, Handa S, Tanaka T, Kaneko MK, Kato Y.
PMab-314: An Anti-Giant Panda Podoplanin Monoclonal Antibody
Monoclon. Antib. Immunodiagn. Immunother.,43(2), 53-58, doi:10.1089/mab.2024.0003, 2024 (PDF)
17. Kaneko MK, Suzuki H, Kato Y.
Establishment of a novel cancer-specific anti-HER2 monoclonal antibody H2Mab-250/H2CasMab-2 for breast cancers
Monoclon. Antib. Immunodiagn. Immunother.,43(2), 35-43,
DOI: 10.1089/mab.2023.0033, 2024 (PDF;online;preprint)
16. Ouchida T, Isoda Y, Nakamura T, Yanaka M, Tanaka T, Handa S, Kaneko MK, Suzuki H, Kato Y.
Establishment of a Novel Anti-Mouse CCR1 Monoclonal Antibody C1Mab-6
Monoclon. Antib. Immunodiagn. Immunother.,43(2), 67-74, https://doi.org/10.1089/mab.2023.0032, 2024 (PDF;preprint)
15. Okada Y, Suzuki H, Tanaka T, Kaneko MK, Kato Y.
Epitope Mapping of an Anti-Mouse CD39 Monoclonal Antibody using PA Scanning and RIEDL Scanning
Monoclon. Antib. Immunodiagn. Immunother.,43(2), 44-52, https://doi.org/10.1089/mab.2023.0029, 2024 (PDF;preprint)
14. Inoue T, Yamamoto Y, Sato K, Nakamura Y, Shimizu Y, Ogawa M, Onodera T, Takahashi Y, Wakita T, Kaneko MK, Fukasawa M, Kato Y, Noguchi K.
Overcoming antibody-resistant SARS-CoV-2 variants with bispecific antibodies constructed using non-neutralizing antibodies
iScience,27(4),109363, DOI:https://doi.org/10.1016/j.isci.2024.109363, 2024 (PDF)
13. Ouchida T, Suzuki H, Tanaka T, Kaneko MK, Kato Y.
Establishment of anti-dog PD-L1 monoclonal antibodies for immunohistochemistry
Monoclon. Antib. Immunodiagn. Immunother., 43(1), 17–23, https://doi.org/10.1089/mab.2023.0014, 2024 (PDF; preprint)
12. Okada Y, Suzuki H, Kaneko MK, Kato Y.
Development of a Sensitive Anti-Mouse CD39 Monoclonal Antibody (C39Mab-1) for Flow Cytometry and Western Blot Anal-yses
Monoclon. Antib. Immunodiagn. Immunother., 43(1), 24–31, https://doi.org/10.1089/mab.2023.0016, 2024 (PDF; preprint)
11. Ouchida T, Suzuki H, Tanaka T, Kaneko MK, Kato Y.
Cx4Mab-1: a Novel Anti-mouse CXCR4 Monoclonal Antibody for Flow Cytometry
Monoclon. Antib. Immunodiagn. Immunother., 43(1), 10–16, DOI: 10.1089/mab.2023.0023, 2024 (PDF;preprint)
10. Kaneko MK, Suzuki H, Ohishi T, Nakamura T, Tanaka T, Kato Y.
A Cancer-specific Monoclonal Antibody against HER2 Exerts Antitumor Activities in Human Breast Cancer Xenograft Models
Int. J. Mol. Sci., 25(3), 1941; https://doi.org/10.3390/ijms25031941, 2024 (PDF)
9. Tanaka T, Suzuki H, Ohishi T, Kaneko MK, Kato Y.
Antitumor activities against breast cancers by an afucosylated anti-HER2 monoclonal antibody H2Mab-77-mG2a-f
Cancer Sci., 115(1), 298-309, https://doi.org/10.1111/cas.16008, 2024 (PDF; preprint)
2023
8. Isoda Y, Kaneko MK, Tanaka T, Suzuki H, Kato Y.
Epitope Mapping of an Anti-Ferret Podoplanin Monoclonal Antibody using the PA Tag-Substituted Analysis
Monoclon. Antib. Immunodiagn. Immunother., 42(6), 189–193, DOI: 10.1089/mab.2023.0026, 2023 (PDF; preprint)
7. Ouchida T, Tanaka T, Suzuki H, Kaneko MK, Kato Y.
PMab-301: An Anti-Giraffe Podoplanin Monoclonal Antibody for Immunohistochemistry
Monoclon. Antib. Immunodiagn. Immunother., 42(6), 209–215, https://doi.org/10.1089/mab.2023.0020, 2023 (PDF; preprint)
6. Suzuki H, Tanaka T, Kudo Y, Tawara M, Hirayama A, Kaneko MK, Kato Y.
A Rat Anti-Mouse CD39 Monoclonal Antibody for flow cytometry
Monoclon. Antib. Immunodiagn. Immunother., 42(6), 203–208, DOI: 10.1089/mab.2023.0018, 2023 (PDF; preprint)
5. Suzuki H, Ohishi T, Tanaka T Kaneko MK, Kato Y.
A Cancer-Specific Monoclonal Antibody against Podocalyxin Exerted Antitumor Activities in Pancreatic Cancer Xenografts
Int. J. Mol. Sci., 25, 161. https://doi.org/10.3390/ijms25010161, 2023 (PDF; preprint)
4. Nanamiya R, Suzuki H, Kaneko MK, Kato Y.
Development of an Anti−EphB4 Monoclonal Antibody for Multiple Applications against Breast Cancers
Monoclon. Antib. Immunodiagn. Immunother.,42(5), 153–156, https://doi.org/10.1089/mab.2023.0015, 2023 (PDF; preprint)
3. Suzuki H, Ohishi T, Kaneko MK, Kato Y.
Humanized and defucosylated antibody against Podoplanin (humLpMab-23-f) exerted antitumor activities in human tumor xenograft models
Cancers, 15(20), 5080; https://doi.org/10.3390/cancers15205080, 2023 (PDF)
2. Suzuki H, Ohishi T, Nanamiya R, Kawada M, Kaneko MK, Kato Y.
Defucosylated Monoclonal Antibody (H2Mab-139-mG2a-f) Exerted Antitumor Activities in Mouse Xenograft Models of Breast Cancers against Human Epidermal Growth Factor Receptor 2
Curr. Issues Mol. Biol., 45(10), 7734-7748; https://doi.org/10.3390/cimb45100488, 2023 (PDF)
1. Ouchida T, Suzuki H, Tanaka T, Kaneko MK, Kato Y.
Development of Highly Sensitive Anti-Mouse HER2 Monoclonal Antibodies for Flow Cytometry
Int. J. Transl. Med., 3(3), 310-320; 2023 (PDF)
