JPWO2015190538A1 - 免疫チェックポイント制御剤の副作用低減方法 - Google Patents
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Abstract
Description
(1) 高い細胞傷害活性を有する抗CD4抗体
(2) 細胞毒成分が結合された、抗CD4抗体又はその抗原結合性断片
WO 2010/074266に記載された方法により、ADCC活性が増強された抗ヒトCD4ヒト化抗体IT1208(可変領域としてWO 2010/074266に記載のHV2及びLV0を含む、サブタイプはIgG1)を作製した。Biacore T100を用いて測定された抗体結合活性はKD(nM)<0.009であり、高い結合活性を有していた。
C57BL/6系統マウス(雌、7週齢、n=8)の右側腹部にマウスメラノーマ細胞株B16F10(5x105 cells/mouse)を皮下移植した後、下記の通りに抗体投与を行なった(Day0=がん細胞移植日)。免疫チェックポイント抗体として、抗PD-1抗体(J43、アンタゴニスト性抗体、BioXcell社製)、抗PD-L1抗体(10F.9G2、BioXcell社製)、抗OX40抗体(OX-86、アゴニスト性抗体、BioXcell社製)、及び抗CTLA-4抗体(9D9、アンタゴニスト性抗体、BioXcell社製)を用いた。
C57BL/6系統マウス(雌、7週齢、n=8)の右側腹部にマウスメラノーマ細胞株B16F10(5x105 cells/mouse)を皮下移植した後、下記の通りに抗体投与を行なった(Day0=がん細胞移植日)。免疫チェックポイント抗体として、抗BTLA抗体(6A6、アンタゴニスト性抗体、BioXcell社製)、抗GITR抗体(DTA-1、アゴニスト性抗体、BioXcell社製)、抗LAG-3抗体(C9B7W、アンタゴニスト性抗体、BioXcell社製)、及び抗TIM-3抗体(RMT3-23、アンタゴニスト性抗体、BioXcell社製)を用いた。
BALB/c系統マウス(雄、8週齢、n=9)の右側腹部にマウス腎がん細胞株Renca(2x105 cells/mouse)を皮下移植した後、下記の通りに抗体投与を行なった(Day0=がん細胞移植日)。免疫チェックポイント抗体として、抗PD-1抗体(J43、アンタゴニスト性抗体、BioXcell社製)、抗PD-L1抗体(10F.9G2、BioXcell社製)を用いた。
BALB/c系統マウス(雌、8週齢、n=10)の乳腺脂肪組織にマウス乳がん細胞株4T1(1x105 cells/mouse)を皮下移植した後、下記の通りに抗体投与を行なった(Day0=がん細胞移植日)。免疫チェックポイント抗体として、抗PD-1抗体(J43、アンタゴニスト性抗体、BioXcell社製)、抗PD-L1抗体(10F.9G2、BioXcell社製)を用いた。
Claims (12)
- 高い細胞傷害活性を有する抗CD4抗体、又は細胞毒成分を結合させた抗CD4抗体若しくはその抗原結合性断片を有効成分として含有する、免疫チェックポイント制御剤の副作用低減剤であって、前記抗CD4抗体は、ヒトCD4に対するヒト型キメラ抗体、ヒト化抗体又はヒト抗体である、副作用低減剤。
- 免疫チェックポイント制御剤は、抑制性の免疫チェックポイント分子に対するアンタゴニスト、及び共刺激性の免疫チェックポイント分子に対するアゴニストから選択される少なくとも1種である、請求項1記載の副作用低減剤。
- 前記抑制性の免疫チェックポイント分子が、PD-1、CTLA-4、LAG-3、TIM-3、BTLA、PD-L1、PD-L2、CD80、CD86、GAL9、及びHVEMからなる群より選択される少なくとも1種であり、前記共刺激性の免疫チェックポイント分子が、CD137、OX40、GITR、CD137L、OX40L、及びTNFSF18からなる群より選択される少なくとも1種である、請求項2記載の副作用低減剤。
- 前記免疫チェックポイント分子が、CTLA-4、PD-L1、及びOX40からなる群より選択される少なくとも1種である、請求項3記載の副作用低減剤。
- 前記免疫チェックポイント分子が、BTLA、GITR、LAG-3、及びTIM-3からなる群より選択される少なくとも1種である、請求項3記載の副作用低減剤。
- 免疫チェックポイント制御剤が、免疫チェックポイント分子に対する抗体である、請求項1ないし5のいずれか1項に記載の副作用低減剤。
- 免疫チェックポイント分子に対する抗体が、抗PD-L1抗体、アンタゴニスト性抗CTLA-4抗体、及びアゴニスト性抗OX40抗体から選択される少なくとも1種である、請求項6記載の副作用低減剤。
- 免疫チェックポイント分子に対する抗体が、アンタゴニスト性抗BTLA抗体、アゴニスト性抗GITR抗体、アンタゴニスト性抗LAG-3抗体、及びアンタゴニスト性抗TIM-3抗体から選択される少なくとも1種である、請求項6記載の副作用低減剤。
- 高い細胞傷害活性を有する抗CD4抗体を有効成分として含有する、請求項1ないし8のいずれか1項に記載の副作用低減剤。
- 前記細胞傷害活性がADCC活性又はCDC活性である、請求項1ないし9のいずれか1項に記載の副作用低減剤。
- 免疫チェックポイント制御剤は、抗がん剤として用いられる、請求項1ないし10のいずれか1項の記載の副作用低減剤。
- 高い細胞傷害活性を有する抗CD4抗体、又は細胞毒成分を結合させた抗CD4抗体若しくはその抗原結合性断片の有効量を患者に投与することを含む、免疫チェックポイント制御剤の副作用を低減する方法であって、前記抗CD4抗体は、ヒトCD4に対するヒト型キメラ抗体、ヒト化抗体又はヒト抗体である、方法。
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PCT/JP2015/066790 WO2015190538A1 (ja) | 2014-06-11 | 2015-06-10 | 免疫チェックポイント制御剤の副作用低減方法 |
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CA2874721A1 (en) | 2012-05-30 | 2013-12-05 | Tomoyuki Igawa | Target tissue-specific antigen-binding molecule |
WO2014163101A1 (ja) | 2013-04-02 | 2014-10-09 | 中外製薬株式会社 | Fc領域改変体 |
KR20220142539A (ko) | 2013-12-04 | 2022-10-21 | 추가이 세이야쿠 가부시키가이샤 | 화합물의 농도에 따라 항원 결합능이 변화되는 항원 결합 분자 및 그의 라이브러리 |
EA035037B1 (ru) | 2013-12-12 | 2020-04-21 | Шанхай Хэнжуй Фармасьютикал Ко., Лтд. | Антитело к pd-1, его антигенсвязывающий фрагмент и их медицинское применение |
EP3338800A1 (en) * | 2014-02-21 | 2018-06-27 | IDAC Theranostics, Inc. | Therapeutic agent for solid cancer |
CN108140909B (zh) * | 2015-07-06 | 2021-07-06 | 阿特罗循环私营有限责任公司 | 从废锂离子电池中回收金属的方法 |
ES2913162T3 (es) * | 2016-01-12 | 2022-05-31 | Univ Chiba Nat Univ Corp | Anticuerpo anti-Myl9 |
CN108883176A (zh) * | 2016-03-28 | 2018-11-23 | 东丽株式会社 | 癌的治疗和/或预防用药物组合物 |
JP6910653B2 (ja) * | 2016-07-01 | 2021-07-28 | 国立大学法人東北大学 | 免疫チェックポイント阻害薬使用における免疫関連副作用の予測方法 |
CA3037380A1 (en) | 2016-10-11 | 2018-04-19 | Agenus Inc. | Anti-lag-3 antibodies and methods of use thereof |
BR112021002037A2 (pt) * | 2018-08-10 | 2021-05-04 | Chugai Seiyaku Kabushiki Kaisha | molécula de ligação de antígeno anti-cd137 e uso da mesma |
TW202120550A (zh) * | 2019-08-08 | 2021-06-01 | 日商小野藥品工業股份有限公司 | 雙特異性蛋白質 |
WO2023127543A1 (ja) * | 2021-12-28 | 2023-07-06 | 国立大学法人大阪大学 | 免疫チェックポイント阻害剤による重篤な有害事象の発生の予測を補助する方法、予測補助装置 |
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EP3156072A4 (en) | 2017-12-20 |
JP6715491B2 (ja) | 2020-07-01 |
US11168137B2 (en) | 2021-11-09 |
EP3156072B1 (en) | 2020-08-19 |
EP3156072A1 (en) | 2017-04-19 |
ES2818800T3 (es) | 2021-04-14 |
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US20170145099A1 (en) | 2017-05-25 |
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