JP2021522866A - がんを予防または治療する効果を奏する新規な菌株 - Google Patents
がんを予防または治療する効果を奏する新規な菌株 Download PDFInfo
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Abstract
【選択図】図2
Description
臨床患者の糞便を用いた腸内微生物の組成の分析
健常人154名と肺がん患者125名から糞便を供されて、腸内微生物の組成に関する研究を行うために、16sシーケンス分析を行った。分析結果に対する患者の病理学的な分類による腸内微生物の分析を行うべく、患者のチャートに従う分類を行った。125名の患者の腫瘍組織において、最も頻繁に生じる非小細胞肺がん(Non−small cell lungc ancer)に属する肺がん2種である扁平上皮がん(Squamous cell carcinoma)と腺がん(Adenocarcinoma)患者のサンプルのみを分類した後、患者が抗がん剤の治療を受けた記録を追跡して抗がん剤の反応に応じて腫瘍の大きさの変化を測定した数値を基準として治療反応具合(PR;Partial Response、SD;Stable Disease、PD;Progressive Disease)に応じた患者のサンプルを分類した。
ビフィドバクテリウム・ビフィダムMG731の分離及び培養
MG731は、健康な乳児の糞便からビフィドバクテリウム種(spp.)に対する選択培地を用いて菌株を分離した。
ビフィドバクテリウム・ビフィダムMG731菌株の腫瘍の増殖抑制効果
ビフィドバクテリウム・ビフィダムMG731が様々ながん細胞株において抗がん効能を示すか否かを確認するために、ヒト由来のがん細胞株を用いてMTTアッセイを行った。
ビフィドバクテリウム・ビフィダムMG731菌株のがん細胞の移動性の低下効果
がん細胞は、正常細胞とは異なり、たとえ細胞に損傷が生じたとしても、増殖しながら移動するという特徴があるため、MG731菌株によりがん細胞の移動性が低下するか否かを確認するために、創傷治癒アッセイ(Wound healing assay)を行った。A549(5×105細胞)及びHCT116(6×105細胞)菌株を6ウェルプレートに付着して細胞が90〜95%増殖した状態になると、チップ(tip)を用いて一定の間隔にて細胞に損傷を加えた。PBSまたはMG731菌株を24時間かけて処理して細胞の移動性の有無を顕微鏡で観察し、その結果を図6に示す。
ビフィドバクテリウム・ビフィダムMG731菌株の血管新生抑制効果
がん細胞の特徴の一つである血管新生過程をMG731菌株が抑えるか否かを確認するために、血管新生に関わる因子に対する発現試験を下記のようにして行った。
ビフィドバクテリウム・ビフィダムMG731菌株の抗炎症効果
MG731菌株の抗炎症効果を確認するために、マウス大食細胞であるRAW264.7細胞にMG731菌株を18時間処理した後、炎症誘発因子であるLPS100ng/mlを6時間処理してRNAを得た。
ビフィドバクテリウム・ビフィダムMG731菌株の抗酸化活性効果
MG731の抗酸化活性を確認するために、A549がん細胞株にMG731を24時間処理した後、H2O2 0.5μMを4時間処理し、DCFDA蛍光染料を用いてFACs装備で細胞内の活性酸素の量を測定し、その結果を図10に示す。
ビフィドバクテリウム・ビフィダムMG731菌株と抗がん剤の併用処理に伴うがん細胞の増殖抑制効果(in vitro実験)
A549、HCT116において、MG731と抗がん剤の併用処理に伴うがん細胞の増殖抑制実験を行った。抗がん剤として、オキサリプラチンまたはペメトレキセドを用いて、下記の方法に従って実験を行った。
ビフィドバクテリウム・ビフィダムMG731菌株と免疫抗がん剤の併用投与に伴う抗腫瘍増進効果(in vitro実験)
ヒトの血液からFicollを用いてPBMC(Peripheral blood mononuclear cells)を収集した後、赤血球溶解緩衝液(RBC lysis buffer)を用いて赤血球を除去して生きている細胞の数を数えて乳酸菌(6×105/50μl/ウェル)が入っている丸底の96ウェルプレートにウェルごとにPBMC 3×104細胞/50μlずつ添加して24時間培養した。
ビフィドバクテリウム・ビフィダムMG731菌株と抗がん剤の併用投与に伴う腫瘍の増殖抑制効果(in vivo実験)
腫瘍モデルを築くに先立ち、マウスに乳酸菌試料を2週間投与して腸内への定着力及び免疫力を高めた後、1群当たりにC57BL/6マウス8匹の右側の尻部近くに2×105 MC38がん細胞を皮下注射することにより、腫瘍誘発モデルを築いた。腫瘍細胞の注入と同時に、3週間(月曜日から土曜日にかけて)乳酸菌試料を前記動物モデルに経口投与した。投与した乳酸菌の試料は、1匹あたりにCFU1×109となるように200μlのPBSに希釈して経口投与した。抗がん剤としてオキサリプラチン(3mg/kg,Sellekchem)または抗PD1(2mg/kg,BioXCell)をがん誘発後に毎週月曜日と木曜日に腹腔注射した。
ビフィドバクテリウム・ビフィダムMG731菌株と抗がん剤の併用投与に伴う抗腫瘍免疫反応の増進効果(in vivo実験)
前記実施例10の結果を踏まえて、腫瘍内に浸透した免疫細胞の分布を確認するために、FACs実験を行うべく、次のような動物実験を行った。
ラクトコッカス・ラクティスGEN3033菌株の分離及び同定
GEN3033菌株を分離するために、年齢41才の健常人の女性から糞便を供された。寄せ集めた新鮮な糞便試料約4gをPBS(Phosphate buffered saline)溶液80mlに添加してボルテックス(vortexing)した後、再懸濁(re−suspension)した。均質化されたサンプルは、同じ溶液に10倍ずつ連続して希釈し、これらの中で、10-5、10-6、10-7、10-8倍希釈されたサンプル200μlを乳酸菌選択培地であるDe Man Rogosa,Sharpe agar(MRSブロス;Difco,USA)培地に塗抹し、37℃の温度下、かつ、好気性の条件下で48時間培養した。固体培地において生成されたそれぞれのコロニーから増幅された16S rRNA遺伝子(1.5kb)を、コロニーPCR方法を用いて取得した。PCRサンプルを精製した後、シーケンシングによって得られた各16S rRNA遺伝子塩基配列をNCBI blastプログラムに代入して近縁種を探索した。
GEN3033菌株に対してAPICHLキット(BioMetrieux Co.France)を用いて糖発酵特性を調べ、その結果を下記表1に示す。
GEN3033菌株の生化学的特性を調べるために、APIZYMキット(BioMetrieux Co.France)を用いて酵素活性特性を調べ、その結果を下記表2に示す。
ラクトコッカス・ラクティスGEN3033菌株の免疫細胞活性効果
GEN3033の免疫活性を確認するために、メモリーT細胞の活性に伴うIFN−γの分泌の変化を下記の方法に従って実験した。
ラクトコッカス・ラクティスGEN3033の抗腫瘍効果(in vitro)
GEN3033が様々ながん細胞株において抗がん効能を示すか否かを確認するために、ヒト由来のがん細胞株11種を用いてCCK−8アッセイを行った。
ラクトコッカス・ラクティスGEN3033菌株の腫瘍の増殖抑制効果(in vivo)
同種のマウス腫瘍モデルは、短時間で腫瘍が急速度で生じて腫瘍の壊死による正確な効能を確認することができないため、腫瘍モデルを築く前に2週間マウスに乳酸菌試料を投与してGEN3033の腸内への定着に伴う免疫活性を誘導した。
ラクトコッカス・ラクティスGEN3033菌株の免疫因子の発現効果
マクロファージと樹状細胞(Dendritic cells)が刺激を受けてT細胞の活性化を引き起こすIL−15とIL−7を分泌する。従って、前記実施例14のマウスの大腸と腫瘍組織から、T細胞の活性を引き起こすIL−15とIL−7の発現を、qPCRを用いて確認した。その結果を図20及び図21に示す。
ラクトコッカス・ラクティスGEN3033菌株と免疫抗がん剤の併用投与
GEN3033と免疫抗がん剤である抗PD1を併用投与したとき、腫瘍の増殖抑制効果を確認するために、次のようにして実験を行った。
ラクトコッカス・ラクティスGEN3033の代謝物の調節
乳酸菌は、腸内への定着により、消化器官において分解される飲食物の分解と吸収を助けて体内の各臓器へ栄養分を供給する。従って、GEN3033による代謝物の変化を確認するために、実施例16の腫瘍モデルにおいて確保したマウスの血清を次のような方法に従って分析した。
免疫抗がん剤耐性肺がんモデルにおけるラクトコッカス・ラクティスGEN3033菌株の腫瘍の増殖抑制効果(in vivo)
実施例17における結果を踏まえて、免疫抗がん剤が効く大腸がんモデルにおいてGEN3033と免疫抗がん剤である抗PD1を併用投与したとき、腫瘍の増殖抑制効果を向上させたことを確認した。これに基づいて、免疫抗がん剤に耐性がある肺がんモデルにおいても、GEN3033及び抗PD1を併用投与したときに抗がん効能が向上するか否かを確認するために、下記の実験を行った。
ラクトコッカス・ラクティスGEN3033と化学抗がん剤または免疫抗がん剤の併用投与に伴う効能の確認
GEN3033が、抗PD1以外の化学抗がん剤または免疫抗がん剤との併用処理においても抗腫瘍効果が著しく増加するか否かをさらに確認するために、下記の実験を行った。
ラクトコッカス・ラクティスGEN3033菌株と免疫抗がん剤の併用投与に伴う抗腫瘍増進効果(in vitro実験)
ヒトの血液からFicollを用いてPBMC(peripheral blood mononuclear cells)を収集した後、赤血球溶解緩衝液(RBC lysis buffer)を用いて赤血球を除去して生きている細胞の数を数えて乳酸菌(3×105/50μl/ウェル)が入っている丸底の96ウェルプレートにウェルごとにPBMC 3×104細胞/50μlずつ添加して24時間培養した。
ビフィドバクテリウム・ビフィダムMG731(Bifidobacterium bifidum MG731)
寄託機関名:韓国生命工学研究院生物資源センター
受託番号:KCTC13452BP
受託日:2018年1月4日
寄託機関名:韓国生命工学研究院生物資源センター
受託番号:KCTC13684BP
受託日:2018年10月25日
ビフィドバクテリウム・ビフィダムMG731の分離及び培養
MG731は、健康な乳児の糞便からビフィドバクテリウム種(spp.)に対する選択培地を用いて菌株を分離した。
ビフィドバクテリウム・ビフィダムMG731菌株の腫瘍の増殖抑制効果
ビフィドバクテリウム・ビフィダムMG731が様々ながん細胞株において抗がん効能を示すか否かを確認するために、ヒト由来のがん細胞株を用いてMTTアッセイを行った。
ビフィドバクテリウム・ビフィダムMG731菌株のがん細胞の移動性の低下効果
がん細胞は、正常細胞とは異なり、たとえ細胞に損傷が生じたとしても、増殖しながら移動するという特徴があるため、MG731菌株によりがん細胞の移動性が低下するか否かを確認するために、創傷治癒アッセイ(Wound healing assay)を行った。A549(5×105細胞)及びHCT116(6×105細胞)菌株を6ウェルプレートに付着して細胞が90〜95%増殖した状態になると、チップ(tip)を用いて一定の間隔にて細胞に損傷を加えた。PBSまたはMG731菌株を24時間かけて処理して細胞の移動性の有無を顕微鏡で観察し、その結果を図2に示す。
ビフィドバクテリウム・ビフィダムMG731菌株の血管新生抑制効果
がん細胞の特徴の一つである血管新生過程をMG731菌株が抑えるか否かを確認するために、血管新生に関わる因子に対する発現試験を下記のようにして行った。
ビフィドバクテリウム・ビフィダムMG731菌株の抗炎症効果
MG731菌株の抗炎症効果を確認するために、マウス大食細胞であるRAW264.7細胞にMG731菌株を18時間処理した後、炎症誘発因子であるLPS100ng/mlを6時間処理してRNAを得た。
ビフィドバクテリウム・ビフィダムMG731菌株の抗酸化活性効果
MG731の抗酸化活性を確認するために、A549がん細胞株にMG731を24時間処理した後、H2O2 0.5μMを4時間処理し、DCFDA蛍光染料を用いてFACs装備で細胞内の活性酸素の量を測定し、その結果を図6に示す。
ビフィドバクテリウム・ビフィダムMG731菌株と抗がん剤の併用処理に伴うがん細胞の増殖抑制効果(in vitro実験)
A549、HCT116において、MG731と抗がん剤の併用処理に伴うがん細胞の増殖抑制実験を行った。抗がん剤として、オキサリプラチンまたはペメトレキセドを用いて、下記の方法に従って実験を行った。
ビフィドバクテリウム・ビフィダムMG731菌株と免疫抗がん剤の併用投与に伴う抗腫瘍増進効果(in vitro実験)
ヒトの血液からFicollを用いてPBMC(Peripheral blood mononuclear cells)を収集した後、赤血球溶解緩衝液(RBC lysis buffer)を用いて赤血球を除去して生きている細胞の数を数えて乳酸菌(6×105/50μl/ウェル)が入っている丸底の96ウェルプレートにウェルごとにPBMC 3×104細胞/50μlずつ添加して24時間培養した。
ビフィドバクテリウム・ビフィダムMG731菌株と抗がん剤の併用投与に伴う腫瘍の増殖抑制効果(in vivo実験)
腫瘍モデルを築くに先立ち、マウスに乳酸菌試料を2週間投与して腸内への定着力及び免疫力を高めた後、1群当たりにC57BL/6マウス8匹の右側の尻部近くに2×105 MC38がん細胞を皮下注射することにより、腫瘍誘発モデルを築いた。腫瘍細胞の注入と同時に、3週間(月曜日から土曜日にかけて)乳酸菌試料を前記動物モデルに経口投与した。投与した乳酸菌の試料は、1匹あたりにCFU1×109となるように200μlのPBSに希釈して経口投与した。抗がん剤としてオキサリプラチン(3mg/kg,Sellekchem)または抗PD1(2mg/kg,BioXCell)をがん誘発後に毎週月曜日と木曜日に腹腔注射した。
ビフィドバクテリウム・ビフィダムMG731菌株と抗がん剤の併用投与に伴う抗腫瘍免疫反応の増進効果(in vivo実験)
前記実施例10の結果を踏まえて、腫瘍内に浸透した免疫細胞の分布を確認するために、FACs実験を行うべく、次のような動物実験を行った。
ラクトコッカス・ラクティスGEN3033菌株の分離及び同定
GEN3033菌株を分離するために、年齢41才の健常人の女性から糞便を供された。寄せ集めた新鮮な糞便試料約4gをPBS(Phosphate buffered saline)溶液80mlに添加してボルテックス(vortexing)した後、再懸濁(re−suspension)した。均質化されたサンプルは、同じ溶液に10倍ずつ連続して希釈し、これらの中で、10-5、10-6、10-7、10-8倍希釈されたサンプル200μlを乳酸菌選択培地であるDe Man Rogosa,Sharpe agar(MRSブロス;Difco,USA)培地に塗抹し、37℃の温度下、かつ、好気性の条件下で48時間培養した。固体培地において生成されたそれぞれのコロニーから増幅された16S rRNA遺伝子(1.5kb)を、コロニーPCR方法を用いて取得した。PCRサンプルを精製した後、シーケンシングによって得られた各16S rRNA遺伝子塩基配列をNCBI blastプログラムに代入して近縁種を探索した。
GEN3033菌株に対してAPICHLキット(BioMetrieux Co.France)を用いて糖発酵特性を調べ、その結果を下記表1に示す。
GEN3033菌株の生化学的特性を調べるために、APIZYMキット(BioMetrieux Co.France)を用いて酵素活性特性を調べ、その結果を下記表2に示す。
ラクトコッカス・ラクティスGEN3033菌株の免疫細胞活性効果
GEN3033の免疫活性を確認するために、メモリーT細胞の活性に伴うIFN−γの分泌の変化を下記の方法に従って実験した。
ラクトコッカス・ラクティスGEN3033の抗腫瘍効果(in vitro)
GEN3033が様々ながん細胞株において抗がん効能を示すか否かを確認するために、ヒト由来のがん細胞株11種を用いてCCK−8アッセイを行った。
ラクトコッカス・ラクティスGEN3033菌株の腫瘍の増殖抑制効果(in vivo)
同種のマウス腫瘍モデルは、短時間で腫瘍が急速度で生じて腫瘍の壊死による正確な効能を確認することができないため、腫瘍モデルを築く前に2週間マウスに乳酸菌試料を投与してGEN3033の腸内への定着に伴う免疫活性を誘導した。
ラクトコッカス・ラクティスGEN3033菌株の免疫因子の発現効果
マクロファージと樹状細胞(Dendritic cells)が刺激を受けてT細胞の活性化を引き起こすIL−15とIL−7を分泌する。従って、前記実施例14のマウスの大腸と腫瘍組織から、T細胞の活性を引き起こすIL−15とIL−7の発現を、qPCRを用いて確認した。その結果を図16及び図17に示す。
ラクトコッカス・ラクティスGEN3033菌株と免疫抗がん剤の併用投与
GEN3033と免疫抗がん剤である抗PD1を併用投与したとき、腫瘍の増殖抑制効果を確認するために、次のようにして実験を行った。
ラクトコッカス・ラクティスGEN3033の代謝物の調節
乳酸菌は、腸内への定着により、消化器官において分解される飲食物の分解と吸収を助けて体内の各臓器へ栄養分を供給する。従って、GEN3033による代謝物の変化を確認するために、実施例16の腫瘍モデルにおいて確保したマウスの血清を次のような方法に従って分析した。
免疫抗がん剤耐性肺がんモデルにおけるラクトコッカス・ラクティスGEN3033菌株の腫瘍の増殖抑制効果(in vivo)
実施例17における結果を踏まえて、免疫抗がん剤が効く大腸がんモデルにおいてGEN3033と免疫抗がん剤である抗PD1を併用投与したとき、腫瘍の増殖抑制効果を向上させたことを確認した。これに基づいて、免疫抗がん剤に耐性がある肺がんモデルにおいても、GEN3033及び抗PD1を併用投与したときに抗がん効能が向上するか否かを確認するために、下記の実験を行った。
ラクトコッカス・ラクティスGEN3033と化学抗がん剤または免疫抗がん剤の併用投与に伴う効能の確認
GEN3033が、抗PD1以外の化学抗がん剤または免疫抗がん剤との併用処理においても抗腫瘍効果が著しく増加するか否かをさらに確認するために、下記の実験を行った。
ラクトコッカス・ラクティスGEN3033菌株と免疫抗がん剤の併用投与に伴う抗腫瘍増進効果(in vitro実験)
ヒトの血液からFicollを用いてPBMC(peripheral blood mononuclear cells)を収集した後、赤血球溶解緩衝液(RBC lysis buffer)を用いて赤血球を除去して生きている細胞の数を数えて乳酸菌(3×105/50μl/ウェル)が入っている丸底の96ウェルプレートにウェルごとにPBMC 3×104細胞/50μlずつ添加して24時間培養した。
ビフィドバクテリウム・ビフィダムMG731(Bifidobacterium bifidum MG731)
寄託機関名:韓国生命工学研究院生物資源センター
受託番号:KCTC13452BP
受託日:2018年1月4日
寄託機関名:韓国生命工学研究院生物資源センター
受託番号:KCTC13684BP
受託日:2018年10月25日
Claims (27)
- ビフィドバクテリウム・ビフィダムMG731(Bifidobacterium bifidum MG731)菌株(KCTC13452BP)。
- ビフィドバクテリウム・ビフィダムMG731(Bifidobacterium bifidum MG731)菌株(KCTC13452BP)を含む、がんの予防または治療のための薬学組成物。
- ビフィドバクテリウム・ビフィダムMG731(Bifidobacterium bifidum MG731)菌株(KCTC13452BP)を含み、前記ビフィドバクテリウム・ビフィダムMG731(Bifidobacterium bifidum MG731)菌株が、抗がん、抗炎症、抗酸化及び免疫増進効果を示すことを特徴とする、がんの予防または治療のための薬学組成物。
- 前記がんは、黒色腫、扁平細胞癌腫、乳がん、頭頚部がん、甲状腺がん、軟部組織肉腫、骨肉腫、精巣がん、前立腺がん、卵巣がん、膀胱がん、皮膚がん、脳腫瘍、血管肉腫、肥滿細胞腫、白血病、リンパ腫、肝臓がん、肺がん、膵臓がん、胃がん、腎臓がん、大腸がん、造血器腫瘍、神経芽細胞腫、類表皮癌腫及びその転移がんからなる群から選ばれるいずれか一種以上であることを特徴とする、請求項2に記載のがんの予防または治療のための薬学組成物。
- 前記がんは、肺がん、大腸がん、胃がん、乳がん及び肝臓がんからなる群から選ばれるいずれか一種以上であることを特徴とする、請求項2に記載のがんの予防または治療のための薬学組成物。
- 前記ビフィドバクテリウム・ビフィダムMG731菌株が、がん細胞の移動性を低下させることにより、抗がん効果を示すことを特徴とする、請求項2に記載のがんの予防または治療のための薬学組成物。
- 前記ビフィドバクテリウム・ビフィダムMG731菌株が、血管増殖因子であるVEGF(Vascular endothelial growth factor)、Ang1(Angiopoietin1)及びAng2(Angiopoietin2)の発現を抑えることにより、抗がん効果を示すことを特徴とする、請求項2に記載のがんの予防または治療のための薬学組成物。
- 前記ビフィドバクテリウム・ビフィダムMG731菌株が、TNF−αの発現を抑えることを特徴とする、請求項3に記載のがんの予防または治療のための薬学組成物。
- ビフィドバクテリウム・ビフィダムMG731(Bifidobacterium bifidum MG731)菌株(KCTC13452BP)を含み、化学抗がん剤または免疫抗がん剤をさらに含むことを特徴とする、がんの予防または治療のための薬学組成物。
- 前記化学抗がん剤は、オキサリプラチン(Oxaliplatin)、ペメトレキセド(Pemetrexed)、シスプラチン(Cisplatin)、ゲムシタビン(Gemcitabine)、カルボプラチン(Carboplatin)、フルオロウラシル(5−FU)、シクロホスファミド(Cyclophosphamide)、パクリタキセル(Paclitaxel)、ビンクリスチン(Vincristine)、エトポシド(Etoposide)及びドキソルビシン(Doxorubicin)からなる群からいずれか一種以上が選ばれることを特徴とする、請求項9に記載のがんの予防または治療のための薬学組成物。
- 前記免疫抗がん剤は、抗PD1、抗PDL1、抗CTLA、抗Tim3及び抗LAG3からなる群からいずれか一種以上が選ばれることを特徴とする、請求項9に記載のがんの予防または治療のための薬学組成物。
- ビフィドバクテリウム・ビフィダムMG731菌株と化学抗がん剤または免疫抗がん剤は、単一の剤形として同時に投与されるか、あるいは、別個の剤形として同時または逐次に投与されることを特徴とする、請求項9に記載のがんの予防または治療のための薬学組成物。
- ビフィドバクテリウム・ビフィダムMG731(Bifidobacterium bifidum MG731)菌株(KCTC13452BP)を含む、がんの予防または改善のための食品組成物。
- ビフィドバクテリウム・ビフィダムMG731(Bifidobacterium bifidum MG731)菌株(KCTC13452BP)を含む、がんの予防または改善のための動物用の飼料組成物。
- ラクトコッカス・ラクティスGEN3033(Lactococcus lactis GEN3033)菌株(KCTC13684BP)。
- ラクトコッカス・ラクティスGEN3033(Lactococcus lactis GEN3033)菌株(KCTC13684BP)を含む、がんの予防または治療のための薬学組成物。
- ラクトコッカス・ラクティスGEN3033(Lactococcus lactis GEN3033)菌株(KCTC13684BP)を含み、前記ラクトコッカス・ラクティスGEN3033(Lactococcus lactis GEN3033)菌株が抗がん及び免疫増進効果を示すことを特徴とする、がんの予防または治療のための薬学組成物。
- 前記がんは、黒色腫、扁平細胞癌腫、乳がん、頭頚部がん、甲状腺がん、軟部組織肉腫、骨肉腫、精巣がん、前立腺がん、卵巣がん、膀胱がん、皮膚がん、脳腫瘍、血管肉腫、肥滿細胞腫、白血病、リンパ腫、肝臓がん、肺がん、膵臓がん、胃がん、腎臓がん、大腸がん、造血器腫瘍、神経芽細胞腫、類表皮癌腫及びその転移がんからなる群から選ばれるいずれか一種以上であることを特徴とする、請求項16に記載のがんの予防または治療のための薬学組成物。
- 前記ラクトコッカス・ラクティスGEN3033菌株が、ガングリオシドGM3(Ganglioside GM3)を増加させることを特徴とする、請求項16に記載のがんの予防または治療のための薬学組成物。
- 前記ラクトコッカス・ラクティスGEN3033菌株が、IFN−γの生成を増加させることを特徴とする、請求項17に記載のがんの予防または治療のための薬学組成物。
- 前記ラクトコッカス・ラクティスGEN3033菌株が、IL−15またはIL−7の発現を増加させることを特徴とする、請求項17に記載のがんの予防または治療のための薬学組成物。
- ラクトコッカス・ラクティスGEN3033(Lactococcus lactis GEN3033)菌株(KCTC13684BP)を含み、化学抗がん剤または免疫抗がん剤をさらに含むことを特徴とする、がんの予防または治療のための薬学組成物。
- 前記化学抗がん剤は、オキサリプラチン(Oxaliplatin)、ペメトレキセド(Pemetrexed)、シスプラチン(Cisplatin)、ゲムシタビン(Gemcitabine)、カルボプラチン(Carboplatin)、フルオロウラシル(5−FU)、シクロホスファミド(Cyclophosphamide)、パクリタキセル(Paclitaxel)、ビンクリスチン(Vincristine)、エトポシド(Etoposide)及びドキソルビシン(Doxorubicin)からなる群からいずれか一種以上が選ばれることを特徴とする、請求項22に記載のがんの予防または治療のための薬学組成物。
- 前記免疫抗がん剤は、抗PD1、抗PDL1、抗CTLA、抗Tim3及び抗LAG3からなる群からいずれか一種以上が選ばれることを特徴とする、請求項22に記載のがんの予防または治療のための薬学組成物。
- ラクトコッカス・ラクティスGEN3033菌株と化学抗がん剤または免疫抗がん剤は、単一の剤形として同時に投与されるか、あるいは、別個の剤形として同時または逐次に投与されることを特徴とする、請求項22に記載のがんの予防または治療のための薬学組成物。
- ラクトコッカス・ラクティスGEN3033(Lactococcus lactis GEN3033)菌株(KCTC13684BP)を含む、がんの予防または改善のための食品組成物。
- ラクトコッカス・ラクティスGEN3033(Lactococcus lactis GEN3033)菌株(KCTC13684BP)を含む、がんの予防または改善のための動物用の飼料組成物。
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