JP4664377B2 - 実験動物における治療抗体の検出 - Google Patents
実験動物における治療抗体の検出 Download PDFInfo
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- JP4664377B2 JP4664377B2 JP2007547356A JP2007547356A JP4664377B2 JP 4664377 B2 JP4664377 B2 JP 4664377B2 JP 2007547356 A JP2007547356 A JP 2007547356A JP 2007547356 A JP2007547356 A JP 2007547356A JP 4664377 B2 JP4664377 B2 JP 4664377B2
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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
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6854—Immunoglobulins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
- C07K16/4283—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig
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- Health & Medical Sciences (AREA)
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- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Medicinal Chemistry (AREA)
- Urology & Nephrology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
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- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Description
ABTS 2,2'-アジノ-ジ-[3-エチルベンズチアゾリンスルホン酸(6)]二アンモニウム塩
BSA ウシ血清アルブミン
ELISA 酵素結合免疫測定法
Fcγ =Fcy=Fcg=Fcガンマ=免疫グロブリンのFcガンマフラグメント
POD(=HRP) 西洋ワサビペルオキシダーゼ
IgG 免疫グロブリンG
DIG(Dig) ジゴキシゲニン
MTP マイクロタイタープレート
OD 光学密度
PBS リン酸緩衝食塩水
SDS ドデシル硫酸ナトリウム
MAK(=Mab) モノクローナル抗体
PAK(=Pab) ポリクローナル抗体
RT 室温
SA ストレプトアビジン
T Tween(登録商標)20
<ヒトIgG> ヒトIgGに対する抗体
特異性の評価
a)MTP-ELISAにおける様々な抗ヒトIgG抗体の使用
マイクロタイタープレート(MTP)(Maxisorb(登録商標),Nunc)を、炭酸緩衝液(pH9.6)で20%に希釈したサル(例えば、カニクイザル)血清およびヒト血清で、それぞれ、室温(RT)で1時間コーティングした。PBS-Tween(登録商標)20で3回洗浄した後に、MTPの全てのウェルをPBS/3%BSAで室温で1時間ブロックした。次いで、MTPのウェルを、異なる抗ヒトIgG抗体(非結合抗ヒトIgG抗体または抗ヒトIgG抗体西洋ワサビペルオキシダーゼ(POD)コンジュゲート(表1を参照されたい))とインキュベートした(1時間;室温)。様々な抗ヒト抗体を、対応する製造業者により推奨されるように使用した。
Biacore(登録商標)2000機器とCM5チップを用いて、全ての測定を行った。このチップへの抗体のコーティングは、標準的なアミンカップリングによって行った。特別の定めのない限り、全てのインキュベーションは、HBS緩衝液(HEPES,NaCl,pH7.4)中で25℃で行った。
全治療抗体を定量するためのMAB<H-Fcγpan>M-R10Z8E9の使用
最初の工程において、ビオチン化MAB<H-Fcγpan>M-R10Z8E9またはポリクローナル抗ヒトFc抗体を、ストレプトアビジンコーティングマイクロタイタープレート(SA-MTP)に結合させた。過剰量の非結合抗体を洗浄によって除去した。同時に、試料/標準、例えば、カニクイザル血清に添加したMAB<IGF-1R>を、ジゴキシゲニン化MAB<H-Fcγpan>M-R10Z8E9-DIG)と1時間プレインキュベートした。その後、混合物を、ビオチン化<ヒトIgG>抗体でコーティングしたSA-MTPウェルに添加し、1時間インキュベートした。洗浄後、結合したジゴキシゲニン化MAB<H-Fcγpan>M-R10Z8E9を抗ジゴキシゲニン抗体で検出した。抗体-酵素コンジュゲートのPODは、ABTS基質の呈色反応を触媒する。シグナルは、405nmの波長(参照波長:490nm)でElisaリーダーによって測定した。それぞれの血清試料の吸光度値は3回繰り返して求めた。
活性ヒト抗体MAB<IL-1R>の定量におけるMAB<H-Fcγpan>M-R10Z8E9の使用
最初の工程において、ビオチン化可溶性ヒトIL-1受容体(h-IL-1R-Bi)を、ストレプトアビジンコーティングマイクロタイタープレート(SA-MTP)に結合させた。過剰量の非結合抗体を洗浄によって除去した。その後、カニクイザル血清に添加したMAB<IL-1R>を、固定化ヒトIL-1受容体に結合させた。結合しなかった物質を洗い落とした後、結合したMAB<1L-1R>は、(a)ジゴキシゲニン化モノクローナル抗ヒトIgG鎖抗体(MAB<H-Fcγpan>M-R10Z8E9-DIG)の後に、西洋ワサビペルオキシダーゼ標識抗ジゴキシゲニン抗体とのインキュベーションを行うことによって、または(b)ポリクローナル抗ヒトFc抗体(Dianova)の後に、洗浄工程を行うことによって検出した。抗体-酵素コンジュゲートに含まれるPODは、ABTS基質の呈色反応を触媒する。シグナルは、405nmの波長(参照波長:490nm)でELISAリーダーによって測定した。それぞれの血清試料の吸光度値は3回繰り返して求めた。
サル血清中の活性MAB<IL-1R>の定量におけるMAB<H-Fcγpan>M-R10Z8E9の使用
最初の工程において、ビオチン化MAB<H-Fcγpan>M-R10Z8E9またはビオチン化ポリクローナル抗ヒトIgGヒトFc(b)抗体を、ストレプトアビジンコーティングマイクロタイタープレート(SA-MTP)のウェルに結合させた。過剰量の非結合抗体を洗浄によって除去した。その後、カニクイザル血清に添加したMAB<IL-1R>を、固定化抗ヒト抗体に結合させた。結合しなかった物質を洗い落とした後、結合したMAB<1L-1R>は、ジゴキシゲニン化可溶性ヒトIL-1受容体(h-IL-1R-Dig)の後に、西洋ワサビペルオキシダーゼ標識抗ジゴキシゲニン抗体とのインキュベーションを行うことによって検出した。抗体-酵素コンジュゲートは、ABTS基質の呈色反応を触媒する。シグナルは、405nmの波長(参照波長:490nm)でELISAリーダーによって測定した。それぞれの血清試料の吸光度値は3回繰り返して求めた。
Claims (6)
- 実験動物から得られた試料において治療抗体を検出する方法であって、以下の工程:
(a)分析する試料を準備する工程、
(b)試料を、受託番号DSM ACC2708のハイブリドーマによって産生されるモノクローナル抗体MAB M-R10Z8E9と同じエピトープに結合する抗体とインキュベートする工程、
(c)任意に、試料を、全治療抗体、活性治療抗体、または抗原結合(antigen-bound)治療抗体を選択的に検出するのに適した試薬とインキュベートする工程、および
(d)(b)または(c)において形成された複合体を、治療抗体の濃度と相関付ける工程
を含み;
前記治療抗体が、ヒト免疫グロブリンクラスGの、ヒトモノクローナル抗体またはヒト化モノクローナル抗体である、方法。 - 実験動物が、マーモセットおよびタマリン、旧世界ザル、コビトキツネザルおよびネズミキツネザル、ギボン(gibbon)および小型類人猿(lesser ape)、キツネザル、ならびにその交雑の科のメンバーを含む群より選択されることをさらなる特徴とする、請求項1記載の方法。
- 全治療抗体が検出される、請求項1または2記載の方法。
- 活性治療抗体が検出される、請求項1または2記載の方法。
- 抗原結合(antigen-bound)治療抗体が検出される、1または2記載の方法。
- 実験動物から得られた試料における全治療抗体、活性治療抗体、または抗原結合(antigen-bound)治療抗体の濃度を測定するための、受託番号DSM ACC2708のハイブリドーマによって産生されるモノクローナル抗体MAB M-R10Z8E9と同じエピトープに結合する抗体の使用であって、
前記全治療抗体、活性治療抗体、または抗原結合(antigen-bound)治療抗体における治療抗体が、ヒト免疫グロブリンクラスGの、ヒトモノクローナル抗体またはヒト化モノクローナル抗体である、使用。
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BR112012005668A2 (pt) * | 2009-10-19 | 2020-10-13 | F. Hoffmann La Roche Ag | '' linhagem celular, anticorpo, uso de um anticorpo, kit, método de detecção de um anticorpo terapêutico, método de determinação imunológica de um anticorpo terapêutico, composição de anticorpo, uso de uma composição de anticorpo'' |
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JP6985572B2 (ja) | 2015-11-09 | 2021-12-22 | 国立大学法人京都工芸繊維大学 | 単鎖抗体のスクリーニング方法及び単鎖抗体 |
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