JP6781252B2 - 多重染色法、及び染色キット - Google Patents
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Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
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Description
(1)細胞を含む検体を固定化した標本において、複数の抗体を用いて検出する多重染色法であって、特定の分子の存在を検出するための抗体と前記特定の分子の変化を検出するための抗体とを用いることを特徴とする多重染色法。
(2)前記特定の分子が治療薬の標的となる細胞抗原タンパク質であって、当該治療薬の効果を判定するために用いることを特徴とする(1)記載の多重染色法。
(3)細胞を含む検体を固定化した標本において、分子の変化を検出するためのキットであって、特定の分子の存在を検出する抗体と前記特定の分子の変化を検出するための少なくとも1つ以上の抗体と、前記特定の分子の存在を検出する抗体と前記特定の分子の変化を検出するための少なくとも1つ以上の抗体とを、夫々識別可能に標識する標識を含むことを特徴とする多重染色キット。
(4)前記特定の分子が治療薬の標的になる細胞抗原タンパク質であって、当該治療薬の効果を判定するために用いることを特徴とする(3)記載の多重染色キット。
(5)前記特定の分子がPD-L1又はPD-L2であって、PD-L1又はPD-L2の存在を検出するための抗体と、PD-L1又はPD-L2のC末領域の変化に伴って認識されない抗体とを含むことを特徴とする(3)又は(4)記載の多重染色キット。
野生型の分子Aと欠失変異を有する分子A’とを同一切片上で同時に染色する方法について説明する(図1、欠失変異体)。野生型の分子Aと欠失変異体A’を発現する細胞を識別する場合には、野生型分子A、変異体分子A’、どちらの分子も確実に認識することのできる抗体aと欠失変異が生じることの多い領域を認識する抗体bを検出に用いれば良い。
染色体に転座が生じ、遺伝子の一部が他の遺伝子と転座により置き換わったことによる融合タンパク質B’を発現する場合について説明する(図1、染色体転座)。抗体cは、転座の有無に関わらず、タンパク質B、B’を認識する抗体を示す。抗体dは野生型タンパク質Bのみ検出し、転座が生じた場合には認識しない抗体を示す。
次に、野生型Cと点突然変異(図中●で示す。)を有する分子C’を区別して染色する方法について説明する(図1、点突然変異)。抗体eは野生型C、点突然変異体C’に関わらず認識する抗体を示す。抗体fは野生型Cのみを認識し、点突然変異体C’は認識しない抗体を示す。
次に、修飾の有無を区別して染色する方法を示す(図1、修飾の有無(リン酸化、糖付加等))。分子によっては活性化に伴ってリン酸化などの修飾を受ける場合がある。また、糖鎖の有無が生体反応に重要な役割をはたしている場合もある。ここでは、リン酸化を受けた分子について説明するが、糖鎖による修飾も同様に検出することができる。
分子によっては、活性化等に伴って、他のタンパク質との相互作用に変化が生じる場合がある。タンパク質Eが単独で存在する場合と、他の分子Xと複合体を形成している場合とを区別して染色する方法について説明する(図1、相互作用(タンパク質等))。
タンパク質は修飾、あるいは複合体形成によって、立体構造自体が大きく変化する場合もある。本実施形態の染色方法で立体構造の変化を捉えることも可能である(図1、立体構造の変化)。
がん細胞では、点突然変異、あるいは欠失変異など複数の変異が同一タンパク質に生じることも多い。本発明の方法は2つの異なる抗体を用いた二重染色だけではなく、3つ以上の変異を区別して染色することも可能である。
以下に本発明の多重染色法を適用した例を実施例として示す。
Claims (5)
- 細胞を含む検体を固定化した標本において、複数の抗体を用いて検出する多重染色法であって、
特定の分子の存在を検出するための抗体と
前記特定の分子の変化を検出するための抗体とを用いることを特徴とする多重染色法。 - 前記特定の分子が治療薬の標的となる細胞抗原タンパク質であって、
当該治療薬の効果を判定するために用いることを特徴とする請求項1記載の多重染色法。 - 細胞を含む検体を固定化した標本において、分子の変化を検出するためのキットであって、
特定の分子の存在を検出する抗体と
前記特定の分子の変化を検出するための少なくとも1つ以上の抗体と、
前記特定の分子の存在を検出する抗体と前記特定の分子の変化を検出するための少なくとも1つ以上の抗体とを、夫々識別可能に標識する標識を含むことを特徴とする多重染色キット。 - 前記特定の分子が治療薬の標的になる細胞抗原タンパク質であって、
当該治療薬の効果を判定するために用いることを特徴とする請求項3記載の多重染色キット。 - 前記特定の分子がPD-L1又はPD-L2であって、
PD-L1又はPD-L2の存在を検出するための抗体と、
PD-L1又はPD-L2のC末領域の変化に伴って認識されない抗体とを含むことを特徴とする請求項3又は4記載の多重染色キット。
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