JP6707505B2 - 腫瘍細胞を検出するためのステロイド受容体アッセイ - Google Patents
腫瘍細胞を検出するためのステロイド受容体アッセイ Download PDFInfo
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Description
a)患者から生物学的試料(血液及び骨髄)を採取する段階と、
b)生物学的試料を循環腫瘍細胞と特異的に反応するリガンドと接触させて他のサンプル成分が実質的に除外されたような、結合された循環腫瘍細胞を生物学的試料の他のサンプル成分から分離させる段階と、
c)段階(b)のサンプルに特異的に結合する少なくとも1種の試薬に、段階(b)のサンプルを接触させる段階と、
d)段階(c)のサンプルを、細胞内のステロイド受容体に対する結合親和力を有する薬剤と接触させる段階と、
e)サンプルを解析して、ステロイド受容体を発現する循環腫瘍細胞の存在を判別する段階と、を含む。
a)循環腫瘍細胞と特異的に反応して他のサンプル成分が実質的に除外されたような、結合された循環腫瘍細胞を生物学的試料の他のサンプル成分から分離させるリガンドと、
b)循環腫瘍細胞及び患者の他のサンプル成分の一方又は両方を特異的に結合する少なくとも1種の試薬と、
c)患者の循環腫瘍細胞においてステロイド受容体に対する結合親和力を有する薬剤と、を含む。
(1) 転移性癌の患者からの循環腫瘍細胞を特徴付ける方法であって、
a)前記患者から生物学的試料(血液及び骨髄)を採取する段階と、
b)他のサンプル成分を実質的に除外して、循環腫瘍細胞と特異的に反応し、そのような結合された循環腫瘍細胞を前記生物学的試料の他のサンプル成分から分離させるリガンドと、前記生物学的試料を接触させる段階と、
c)段階(b)の前記サンプルに特異的に結合する少なくとも1種の試薬に、段階(b)の前記サンプルを接触させる段階と、
d)段階(c)の前記サンプルを、細胞内のステロイド受容体に対する結合親和力を有する薬剤と接触させる段階と、
e)前記サンプルを解析して、ステロイド受容体を発現する循環腫瘍細胞の存在を判別する段階と、
を含む方法。
(2) 前記ステロイド受容体を発現する循環腫瘍細胞の数を特定する段階を更に含む、実施態様1に記載の方法。
(3) 循環腫瘍細胞と特異的に反応する薬剤を、前記循環腫瘍細胞内の前記ステロイド受容体のN末端領域及びC末端領域の一方又は両方に連結する、実施態様1に記載の方法。
(4) 前記試薬がDAPI、サイトケラチン及びCD45陰性(CD45 neg)からなる群より選択される、実施態様1に記載の方法。
(5) 前記リガンドが前記腫瘍細胞上の上皮細胞接着エピトープに特異的に結合する、実施態様1に記載の方法。
(7) 段階(e)の前記サンプルが、マルチパラメーターフローサイトメトリー、免疫蛍光顕微鏡法、レーザー走査サイトメトリー、明視野に基づく画像解析、スペクトル画像解析、手動細胞解析、CELLSTRACKS(登録商標)解析、及び自動細胞解析からなる群から選択される少なくとも1つの方法によって解析される、実施態様1に記載の方法。
(8) 段階(b)の前記生成物を磁場にさらす段階を更に含む、実施態様6に記載の方法。
(9) 前記磁気応答粒子がコロイド状である、実施態様6に記載の方法。
(10) 前記薬剤がID5、CF11、E115(rbモノ)、ER119.3、及びSP−1(rbモノ(rb mono))からなる群より選択される抗体である、実施態様1に記載の方法。
(12) ステロイド受容体を発現する循環腫瘍細胞の存在について、患者サンプルをスクリーニングするための試験キットであって、
a)他のサンプル成分を実質的に除外して、循環腫瘍細胞と特異的に反応して、そのような結合された循環腫瘍細胞を前記生物学的試料の他のサンプル成分から分離させるリガンドと、
b)循環腫瘍細胞及び患者の他のサンプル成分の一方又は両方に特異的に結合する少なくとも1種の試薬と、
c)前記患者の前記循環腫瘍細胞においてステロイド受容体に対する結合親和力を有する薬剤と、
を含む試験キット。
Claims (17)
- 転移性乳癌の患者からの循環腫瘍細胞の特徴付けをするためのキットの製造における成分i)、ii)、及びiii)、
i)抗EpCAM抗体と磁気応答粒子との複合体であって、前記複合体は、生物学的試料中の前記循環腫瘍細胞と特異的に反応して前記生物学的試料の他のサンプル成分を実質的に除外し、結合された前記循環腫瘍細胞を前記生物学的試料の前記他のサンプル成分から分離させる、複合体、
ii)前記患者の前記循環腫瘍細胞及び前記他のサンプル成分の一方又は両方に特異的に結合する少なくとも1種の試薬であって、DAPI、蛍光染料に接合された抗サイトケラチン抗体、およびCD45に特異的に結合する蛍光接合体、からなる群から選択される試薬、及び、
iii)エストロゲン受容体のN末端領域及びC末端領域の一方または両方に対する抗体であって、前記抗体が、H222、ID5、E115(rbモノ)、及びSP−1(rbモノ)からなる群から選択される、抗体、
の使用であって、前記特徴付けは、
(a)血液及び骨髄サンプルから選択された、前記患者からの前記生物学的試料を提供する段階と、
(b)(i)の前記複合体と、前記段階(a)の前記生物学的試料を接触させる段階と、
(c)段階(b)の生成物を磁場にさらして、結合した前記循環腫瘍細胞を前記段階(a)の前記生物学的試料の前記他のサンプル成分から分離し、減少した容積の生成物を得る段階と、
(d)段階(c)の生成物中の前記結合した循環腫瘍細胞を、(ii)の前記少なくとも1種の試薬と接触させる段階と、
(e)段階(d)の生成物中の前記結合した循環腫瘍細胞を、(iii)の前記抗体と接触させる段階と、
(f)前記エストロゲン受容体を発現する前記循環腫瘍細胞の存在を決定するために段階(e)の生成物を解析する段階と、
(g)段階(e)の生成物中の、前記エストロゲン受容体を発現する前記循環腫瘍細胞の数を決定する段階と、を含む、使用。 - 段階(f)における解析は、マルチパラメーターフローサイトメトリー、免疫蛍光顕微鏡法、レーザー走査サイトメトリー、明視野に基づく画像解析、スペクトル画像解析、手動細胞解析、CELLSTRACKS(登録商標)解析、及び自動細胞解析からなる群から選択される少なくとも1つの方法によって行われる、請求項1に記載の使用。
- 前記磁気応答粒子がコロイド状である、請求項1に記載の使用。
- 前記エストロゲン受容体の前記N末端領域及び前記C末端領域の一方または両方に対する抗体は前記E115(rbモノ)である、請求項1に記載の使用。
- 前記抗EpCAM抗体はVU−1D9である、請求項1に記載の使用。
- 前記抗EpCAM抗体であるVU−1D9は前記磁気応答粒子に接合する、請求項5に記載の使用。
- 段階(c)の生成物を、HER/2neuに特異的な抗体と接触させる段階を、段階(d)がさらに含む、請求項1に記載の使用。
- 前記HER/2neuに特異的な抗体が、モノクローナル抗体Her−81である、請求項7に記載の使用。
- エストロゲン受容体を発現する循環腫瘍細胞の存在について、転移性乳癌患者のサンプルをスクリーニングするための試験キットであって、
a)抗EpCAM抗体と磁気応答粒子との複合体であって、前記複合体は前記循環腫瘍細胞と特異的に反応して、患者サンプルの他のサンプル成分を実質的に除外し、結合した循環腫瘍細胞を前記患者サンプルの前記他のサンプル成分から分離させる、複合体、
b)患者の前記循環腫瘍細胞及び前記他のサンプル成分の一方又は両方に特異的に結合する少なくとも1つの試薬であって、DAPI、蛍光染料に接合した抗サイトケラチン抗体、及びCD45に特異的に結合する蛍光接合体からなる群から選択される試薬、及び、
c)前記患者の前記循環腫瘍細胞内の前記エストロゲン受容体のN末端領域及びC末端領域のいずれか一方又は両方に対する抗体であって、H222、ID5、E115(rbモノ)、及びSP−1(rbモノ)からなる群から選択される抗体を含む、試薬キット。 - 転移性癌の患者からの循環腫瘍細胞を特徴付けるためのin vitro方法であって、
(a)血液及び骨髄サンプルから選択された、前記患者からの生物学的試料を提供する段階と、
(b)前記生物学的試料を前記循環腫瘍細胞と特異的に反応するリガンドと接触させて、前記生物学的試料の前記循環腫瘍細胞以外のサンプル成分を実質的に排除して、結合した前記循環腫瘍細胞を前記生物学的試料の前記循環腫瘍細胞以外の前記サンプル成分から分離させる段階であって、前記リガンドは、磁気応答粒子に接合した抗EpCAM抗体である、段階と、
(c)段階(b)の生成物を磁場にさらし、結合した前記循環腫瘍細胞を含む、減少した容積の生成物を得る段階と、
(d)段階(c)の生成物中の前記循環腫瘍細胞を、段階(b)の生成物中の前記循環腫瘍細胞に特異的に結合する少なくとも1種の試薬と接触させる段階であって、前記少なくとも1種の試薬は、DAPI、蛍光染料に接合した抗サイトケラチン抗体、及びCD45に特異的に結合する蛍光接合体からなる群から選択される、段階と、
(e)段階(d)の生成物中の前記循環腫瘍細胞を、エストロゲン受容体のN末端領域及びC末端領域の一方又は両方に対する結合親和力を有する薬剤と接触させる段階であって、前記薬剤が、H222、ID5、E115(rbモノ)、及びSP−1(rbモノ)からなる群から選択される段階と、
(f)前記エストロゲン受容体を発現する前記循環腫瘍細胞の存在を決定するために段階(e)の生成物を解析する段階と、
(g)段階(e)の生成物中における前記エストロゲン受容体を発現する前記循環腫瘍細胞の数を決定する段階と、を含むin vitro方法。 - 段階(f)における解析は、マルチパラメーターフローサイトメトリー、免疫蛍光顕微鏡法、レーザー走査サイトメトリー、明視野に基づく画像解析、スペクトル画像解析、手動細胞解析、免疫磁気的に選択された循環腫瘍細胞(CTC)の計数のための半自動蛍光解析、及び自動細胞解析からなる群から選択される少なくとも1つの方法によって行われる、請求項10に記載のin vitro方法。
- 前記磁気応答粒子がコロイド状である、請求項10に記載のin vitro方法。
- 前記エストロゲン受容体の前記N末端領域及び前記C末端領域の一方または両方に対する結合親和力を有する前記薬剤は前記E115(rbモノ)である、請求項10に記載のin vitro方法。
- 前記抗EpCAM抗体はVU−1D9である、請求項10に記載のin vitro方法。
- 前記抗EpCAM抗体であるVU−1D9は前記磁気応答粒子に接合する、請求項10に記載のin vitro方法。
- 段階(c)の生成物を、HER/2neuに特異的な抗体と接触させる段階を、段階(d)がさらに含む、請求項10に記載のin vitro方法。
- 前記HER/2neuに特異的な抗体が、モノクローナル抗体Her−81である、請求項16に記載のin vitro方法。
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