CN1036793A - 人体癌细胞新型类粘性糖蛋白表面抗原的专一性单克隆抗体 - Google Patents

人体癌细胞新型类粘性糖蛋白表面抗原的专一性单克隆抗体 Download PDF

Info

Publication number
CN1036793A
CN1036793A CN89102008A CN89102008A CN1036793A CN 1036793 A CN1036793 A CN 1036793A CN 89102008 A CN89102008 A CN 89102008A CN 89102008 A CN89102008 A CN 89102008A CN 1036793 A CN1036793 A CN 1036793A
Authority
CN
China
Prior art keywords
monoclonal antibody
antigen
bre
cell
molecular weight
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN89102008A
Other languages
English (en)
Inventor
罗伯特·L·瑟林尼
吉利·A·皮特森
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
John Muir Cancer & Aging Institute
Muir John Cancer and Aging Institute
Original Assignee
John Muir Cancer & Aging Institute
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by John Muir Cancer & Aging Institute filed Critical John Muir Cancer & Aging Institute
Publication of CN1036793A publication Critical patent/CN1036793A/zh
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3015—Breast
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
    • A61K47/6855—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from breast cancer cell
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1045—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1045—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants
    • A61K51/1051—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants the tumor cell being from breast, e.g. the antibody being herceptin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2123/00—Preparations for testing in vivo
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Cell Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Oncology (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Optics & Photonics (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (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)

Abstract

一种专一地与人乳腺癌细胞表面上的特定抗原 决定因子结合的单克隆抗体，但它不与正常的人乳腺 组织结合。该抗原特征在于其是分子量大于400000 道尔顿的类粘性糖蛋白复合物，而且该单克隆抗体能 用来诊断和治疗人体乳腺癌。

Description

本发明是有关能与人体癌细胞表面抗原结合的单克隆抗体的发明，更具体地说，本发明涉及一种对乳腺癌及其它组织的某些癌上的高分子量类粘性糖蛋白复合物具有活性的单克隆抗体，而它不会与人体乳腺正常上皮细胞结合。
已有制得几种能识别人体乳腺正常上皮细胞表面上的高分子量的类粘性糖蛋白复合物的单克隆抗体，例如参见Peterson等人，Imperial    Cancer    Research    Fund，London，England，March    2-3（1981）;Taylor-Papadimi-triou等人，Somatic    Cell    Genetics，9：415-427（1983）。其它研究者用人体乳脂肪球作为免疫试剂〔Taylor-Papadimitrisn等人，Int.J.Cancer，28：17-21（1981）;Ceriani等人，Somatic    Cell    Genetics，9∶415-427（1983）〕和用各种乳腺肿癌细胞作为免疫试剂〔Papsidero等人，Cancer    Research，43：1741-1747（1983）;Kufe等人，Hybridoma，3：223-232（1984）;Frank等人，J.Bid.Response    Mod.，4：273-286（1985）;Colcher等人，Rroc.Natl.Acad.Sci.USA，78：3199-3203（1981）;Foster等人，Virchons    Arch，394：279-293（1982）;Ellis等人，Histopathologg，8：501-516（1984）;Ashall等人，Lancet，2：1-11（1982）〕制得单克隆抗体。根据免疫原的制备情况，这些单克隆抗体能识别分子量约250，000道尔顿至一百万道尔顿以上的类粘性糖蛋白〔参见Shimigu等人，Biochem.J.，233：725-730（1986）〕。
对人体乳脂肪球膜的高分子量类粘性糖蛋白进行生化分析，结果发现这些糖蛋白为至少由三种不同组份构成的复合物，这些组分至少代表三种不同的分子〔参见Shimign等人，Biochem    J.，233：725-730（1986）〕，因此，人体乳脂肪球膜的类粘性糖蛋白被认为是高分子复合物，由于其尺寸较大则有许多个抗原决定基。已经制得的单克隆抗体能与正常和恶性乳腺细胞表面上的类粘性糖蛋结合，如Ceriani等人在Somatic    Cell    Genetics，9：415-427（1983）中所述的Mc5单克隆抗体。此外，对豚鼠乳脂肪球膜专一性的单克隆抗体D-274也被用来确定400，000道尔顿以上的类粘性糖蛋白在人乳腺良性纤维胆囊疾病与渗透导管癌中的分布〔参见Greenwalt等人，Am.J.Pathol.，118：351-359（1985）〕。
现有技术中的单克隆抗体能与正常乳腺细胞、乳腺癌以及其它组织的某些上皮细胞相结合，但是这些单克隆抗体对于正常乳腺组织以及乳腺癌具有结合专一性。倘若能提供一种只与乳腺癌和其它组织的一些癌表面上表达的特定抗原决定基结合而不与人体乳腺正常上皮细胞上表达的抗原决定基结合的单克隆抗体，那将是十分有利的。
因此，这里将记载一种仅与人体乳腺癌细胞上的新型类粘性糖蛋白抗原结合而不与正常的人体乳腺上皮细胞结合的单克隆抗体。该单克隆抗体识别乳房、卵巢、子宫内膜、肺和胰的腺癌细胞，但不与心脏、胃肠器官系统、脑垂体、前列腺、间质组织、肝、甲状旁腺、乳腺、脾、甲状腺、睾丸、或卵巢的正常上皮细胞相结合。该单克隆抗体一般不会与腺瘤结合。
由该单克隆抗体识别的抗原用“BrE1”表示，其特征在于分子量大于400，000道尔顿。BrE1单克隆抗体的专一性使得它在治疗乳腺癌时，尤其对于世界各地已确认的大多数乳腺癌来说有利于诊断并进行可能的治疗。
用正常的脱脂后的人体脂肪球作为免疫试剂制得BrE1单克隆抗体。
采用常规方法〔如Kohler和Milstein，Nature，256：495-497（1975）所述〕制备本发明所述的单克隆抗体。用完整的脱脂人体乳脂肪球（HMFG）〔其制备如Ceriani等人，Proc.Natl.Acad.Sci.USA，74：582-586（1977）所述〕对宿主动物进行免疫，该宿主动物是Balb/c小鼠，经过一定时间的培养以后，收获该鼠的脾细胞。
而后采用已知的聚乙烯乙二醇技术将收获的脾细胞与P3-NS1/I-Ag4-1鼠骨髓瘤融合，采用固相放射性免疫平面结合分析法及ELISA分析法筛选出能产生本发明的单克隆抗体的杂交瘤或杂交细胞系，上述两种方法均是在微滴定度板〔如Ceriani等人，Somatio Cell Genetics，9：415-427（1983）中所述〕中利用HMFG和HMFG组分进行的，此后在人体乳腺癌组织细胞系MCF-7〔参见Soule等人，J.Natl.Cancer Inst.51：1409-1413（1973）〕以及颈癌、结肠癌和淋巴癌的其它细胞系（Bris 8）上筛选出对HMFG阳性的井。使人体乳腺癌细胞系染色的单克隆抗体则被识别出来，从而将产生该抗体的杂交细胞分离，该单克隆抗体在这里表示为抗-BrE1，采用Western印迹试验〔如Towbin等人，PNAS，76：4350-4354（1979）所述〕和固相结合分析法〔如Ceriani等人，Monoclonal Antibodies and Functional Cell Lines，Plenum Press，New York，398-402（1984）所述〕通过BrE1单克隆抗体鉴定抗原的分子量或Mr。
在Western印迹试验过程中，由7%聚丙烯酰胺凝胶电泳分离HMFG，然后再电沾到硝化纤维纸上，将该硝化纤维割成条状并培养，分子量大的样品随即在凝胶平行截面上泳动。
在固相结合分析过程中，将HMFG在7%聚丙烯酰胺凝胶上进行电泳〔如Laemmli VK，Nature，227：680（1970）所述〕，将凝胶线条切成片，将切片洗提，并将洗提物在微滴定度板上干燥，通过放射性免疫结合分析技术测定单克隆抗体的结合情况。当在Western印迹试验及固相结合分析过程中对HMFG进行电泳时，该单克隆抗体BrE1仅能识别一种在聚丙烯酰胺凝胶原点上的物质。因此，由该单克隆抗体BrE1识别的类粘性糖蛋白抗原停留在原点上而不会穿透该聚丙烯酰胺凝胶。然后采用前面所述的固相结合分析法将HMFG在小于7%的聚丙酰胺凝胶上进行电泳，利用大分子量标准试样就能计算出由单克隆抗体BrE1识别的类粘性糖蛋白抗原的分子量。估计该抗原的分子量超过400，000道尔顿，对BrE1和Mc5单克隆抗体对该糖蛋白抗原的竞争能力进行了研究。结果发现该单克隆抗体BrE1不与Mc5抗体结合相同的抗原决定基进行竞争结合。
在用BrE1单克隆抗体分析含有乳腺癌细胞或分子的体液时，我们发现它与分子量低于400，000道尔顿的糖蛋白分子也发生了结合。对此我们假定BrE1单克隆抗体所结合的高分子量的类粘性糖蛋白抗原在体液中已变性了，例如裂解成片了。这表明BrE1单克隆抗体能识别位于高分子量抗原上的以及用来解释这一现象的分子或碎片上的普通抗原决定基。因此，尽管BrE1单克隆抗体是专一地与分子量大于400，000道尔顿的抗原结合，但它也会与这类分子上发现的抗原的普通抗原决定基相结合，这是有可能的，因为该高分子量的抗原是一种分子的复合物。
BrE1单克隆抗原同型抗原经小鼠免疫球蛋白药箱确认为是IgG2a。
为了进一步突出组织特异性，更广泛地测定BrE1单克隆抗体与组织切片的结合性能。采用常规免疫过氧化酶分析法来分析该抗体与人体正常和癌组织的组织切片的结合性能。所述的组织以多种肿瘤组织块形式制备〔如Battifora H.，Lab.Invest.，55：244-248（1986）所述〕，通过将这些组织包在腹膜或肠中以及包埋在石蜡中，从固定组织条带制备得到每一种组织块，然后在制备过程中将该组织块切片以供研究结合性能用，这样用一次染色就能分析大量不同的组织。
用来使BrE1单克隆抗体特征化的乳腺块含有来自正常乳腺的21种不同的样本、22种腺瘤、33种乳腺癌。BrE1单克隆抗体与乳腺癌结合，但不与所测定的任何正常乳腺切片结合，也不与腺瘤结合，这种结合之所以发生，是因为该免疫原-HMFG-不是由正常的乳腺上皮细胞膜获得的。这一结果表明乳腺癌中表达的转化表现型或一较早前体在免疫的HMFG中已经出现。
BrE1单克隆抗体还被用来对除乳腺癌以外的许多不同的正常组织和肿瘤组织进行试验，与利用乳腺块的BrE1性能相反的是，该BrE1单克隆抗体与正常的肺组织和大多数肺癌结合，而且它均等地与卵巢及乳腺癌结合，但不与正常的卵巢或乳腺结合。
BrE1单克隆抗体不会使下列肿瘤染色：鼻咽瘤、黑瘤、神经母细胞瘤、前列腺瘤、甲状旁腺瘤、腹膜、脾、肾、甲状腺或胚的肿瘤。此外，染色的非乳腺肿瘤大多是卵巢、子官内膜、肺和胰腺的腺瘤。
能产生BrE1单克隆抗体的杂交细胞样品于1988年6月9日在American Type Cultune Collection，Rook-Ville，Margland 20852寄存，寄存号为A.T.C.C.HB9738。
BrE1单克隆抗体是独一无二的，这是因为它对存在于乳腺癌表面的高分子量的类粘性糖蛋白复合物具有特殊的专一性结合而对正常的乳腺上皮细胞则无专一性。因此，该BrE1抗体对诊断人体乳腺癌特别有用，举例来说，可以用一种可见的标记物如染色剂、萤光物质或一种放射性示踪物对该单克隆抗体进行标记，以显示肿瘤。合适的示踪物是锢111，锝97，碘131。此外，BrE1单克隆抗体与一种毒素结合可以用来进行治疗。所述毒素如它能溶解与BrE1单克隆抗体结合的肿瘤细胞，但不会对正常的乳腺上皮组织细胞起作用。同样利用一种合适的放射性标记物如锢111，锝99或碘131的方法也是可行的。
利用BrE1单克隆抗体的免疫分析可进行体外诊断，分析过程中用微球体与涂层并适当包埋或标记的抗原或抗体结合。标记物或包埋物可以根据这里所述的和本领域所熟知方法进行变换。体外使用时，可以将BrE1抗体放入配有其它组分的分析药箱中，从而可以根据所附文献中的分析方法对生物试样进行分析。同样，对于体内使用也是可行的（不管是用来诊断还是用来治疗）。该分析可以和流动细胞测量方法一起用来研究细胞分化及细胞型专一性，也可以用它作为肿瘤组织病理的一种预防工具。举出这些体内、体外使用的例子并不排除BrE1单克隆抗体的其它用途。

Claims (28)

1、一种采用杂交瘤技术制备的细胞系，它能产生一种与人乳腺癌细胞抗原结合的，但不与正常的人乳腺组织细胞结合的单克隆抗体。
2、根据权利要求1所述的细胞系，其中所说的抗原人乳腺癌细胞的类粘性糖蛋白分子复合物上表达。
3、根据权利要求2所述的细胞系，其中所说的抗原其特征在于具有分子量在400000道尔顿以上的BrE1抗原，而且能产生对BrE1抗原的小鼠IgG2a同型抗体。
4、根据权利要求3所述的细胞系，其中所说的抗原有一个分子量小于400000道尔顿的分子上抗原决定基，能与所说的单克隆抗体结合。
5、根据权利要求2所述的细胞系，其中所说的抗原其特征在于BrE1抗原的分子量大于400000道尔顿，而且在分子量小于400000道尔顿的分子上有一个抗原决定基，该单克隆抗体也能与该抗原决定基结合。
6、根据权利要求1所述的细胞系，其中所说的产生细胞的单克隆抗体是从用正常的脱脂人体乳脂肪球免疫过的小鼠身上获得的。
7、根据权利要求1所述的细胞系，其中所说的产生细胞的单克隆抗体是用脱脂人体脂肪球免疫过的鼠脾细胞。
8、根据权利要求7所述的细胞系，其中所述的鼠脾细胞是用正常完整的人体乳脂肪球膜免疫过的。
9、根据权利要求7所述的细胞系，其中所说的鼠脾细胞是用正常的人体乳脂肪球组分免疫过的。
10、根据权利要求2所述的细胞系，其中所说的抗原通过腺瘤上的单克隆抗体是基本看不到的。
11、根据权利要求2所述的细胞系，其中所说的单克隆抗体能识别肺和肾正常的上皮细胞。
12、采用杂交瘤技术制得的细胞系，它具有寄存在American  Type  Culture  Collection  Kockville，Maryland.寄存号为A.T.C.C.No.HB  9738样品的基本特征。
13、一种单克隆抗体，它仅与人乳腺肿瘤细胞的高分子量的类粘性糖蛋白复合物分子上的一个抗原决定因子结合，其特征在于：
A.通过对该抗原进行电泳并将其泳动特性与分子量已知的标记蛋白的泳动相比得知所述抗体是分子量大于400，000道尔顿的BrE1;
B.它在肿瘤细胞的表面或细胞质上表达;
C.它在正常的人乳腺组织上基本不可见;
D.它具有IgG2a同型抗原。
14、根据权利要求13所述的单克隆抗体，其中所说的抗原还在分子量小于400000道尔顿的分子上有一个抗原决定基与所说的单克隆抗体结合。
15、根据权利要求13所述的通过杂交瘤技术制得的单克隆抗体，它具有寄存在American  Type  Culture  Collection  Kockville，Maryland，寄存号为A.T.C.C.No.HB  9738样品的基本特征。
16、根据权利要求13所述的单克隆抗体，其中所说的BrE1抗原在腺瘤上基本不可见。
17、根据权利要求13所述的单克隆抗体，其中所说的BrE1抗原在卵巢、子宫内膜、肺、胰和乳腺腺癌细胞上皮细胞表面上是可见的。
18、一种检测含有人类癌细胞或分子BrE1抗原的生物样本中的BrE1抗体的方法，它包括使所说的生物试样与专一地和BrE1抗原（与一标记物相连）结合的单克隆抗体接触一段时间，其接触条件需是以在所说的单克隆抗体和抗原之间形成免疫复合物;在基质反应可见的产物上检测所述的免疫复合物。
19、根据权利要求18所述的方法，其中所说被检测的单克隆抗体和抗原免疫复合物包括一个含有与BrE1单克隆抗体结合的普通抗原决定基的抗原分子。
20、根据权利要求18所述的方法，其中所说的标记物是涂覆在微球体上的。
21、根据权利要求18所述的方法，其中所说的标记物选自放射性元素，萤光染料和酶。
22、一种小鼠IgG2a同型抗原的鼠单克隆抗体，它能专一地与BrE1抗原结合，其中的抗原与一种化学治疗的，光活性毒素或放射性试剂结合。
23、一种在含BrE1抗原的人乳腺癌细胞或分子的生物试样中测定是否存在BrE1抗原的方法，它包括使所说的生物试样和标记了的能专一地与BrE1抗原结合的单克隆抗体接触一段时间，其接触条件需足以在该单克隆抗体和所说的抗原之间产生免疫反应，若需要，再检测免疫复合物。
24、根据权利要求23所述的方法，其中所说的标记物选自染料、萤光染料、放射性元素和酶。
25、一种在怀疑患有肿瘤的病人身上检测乳腺癌的方法，它包括将专一地与BrE1抗原结合的单克隆抗体（用一种放射性元素衍生）注入到所说的病人身上并过一段时间，其条件需足以在所说的单克隆抗体和所说肿瘤之间形成免疫复合物;用衍生出来的单克隆抗体标记所说肿瘤以检测所说肿瘤。
26、根据权利要求25所述的方法，其中所说的放射性试剂是锢111、锝99、或碘131。
27、在怀疑患有肿瘤的病人身上杀死乳腺瘤肿瘤细胞的方法，它包括向所说病人注入一种单克隆抗体-毒性试剂混合物并保持一定时间，其中的抗体专一地与BrE1抗原结合，其条件需足以在所说抗体-毒性试剂混合物之间形成免疫络合物，引起肿瘤细胞死亡。
28、根据权利要求27所述的方法，其中所说的毒性试剂是放射性试剂。
CN89102008A 1988-02-08 1989-02-08 人体癌细胞新型类粘性糖蛋白表面抗原的专一性单克隆抗体 Pending CN1036793A (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US15307288A 1988-02-08 1988-02-08
US07/153,072 1988-02-08
US27199488A 1988-11-16 1988-11-16
US07/271,994 1988-11-16

Publications (1)

Publication Number Publication Date
CN1036793A true CN1036793A (zh) 1989-11-01

Family

ID=26850130

Family Applications (1)

Application Number Title Priority Date Filing Date
CN89102008A Pending CN1036793A (zh) 1988-02-08 1989-02-08 人体癌细胞新型类粘性糖蛋白表面抗原的专一性单克隆抗体

Country Status (6)

Country Link
EP (1) EP0401247A4 (zh)
JP (1) JPH03503120A (zh)
CN (1) CN1036793A (zh)
AU (1) AU3049189A (zh)
ES (1) ES2012997A6 (zh)
WO (1) WO1989007268A1 (zh)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU625856B2 (en) * 1987-07-15 1992-07-16 United States of America, as represented by the Secretary, U.S. Department of Commerce, The Second generation monoclonal antibodies having binding specificity to tag-72 and human carcinomas and methods for employing the same
US5075219A (en) * 1989-04-05 1991-12-24 John Muir Cancer & Aging Institute Monoclonal antibody which recognizes a specific glycoprotein of a human milk-fat globule membrane mucin antigen and said mucin antigen
GB9019553D0 (en) * 1990-09-07 1990-10-24 Unilever Plc Specific binding agents
FR2693233B1 (fr) * 1992-07-02 1994-08-19 Inst Francais Du Petrole Dispositif de contrôle de l'injection pneumatique d'un mélange carbure dans un moteur à combustion interne à deux temps et utilisation associée.
GB2273099A (en) * 1992-11-10 1994-06-08 Asta Medica Ag Glycoprotein encoded by a human endogenous retrovirus K envelope gene
WO1994018562A1 (en) * 1993-02-05 1994-08-18 Epigen, Inc. Human carcinoma antigen (hca), hca antibodies, hca immunoassays, methods of imaging and therapy
US6949244B1 (en) 1995-12-20 2005-09-27 The Board Of Trustees Of The University Of Kentucky Murine monoclonal anti-idiotype antibody 11D10 and methods of use thereof
US6274143B1 (en) 1997-06-13 2001-08-14 Malaya Chatterjee Methods of delaying development of HMFG-associated tumors using anti-idiotype antibody 11D10
US9696320B2 (en) * 2010-09-17 2017-07-04 National Institute Of Advanced Industrial Science And Technology Lung cancer differential marker

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4522918A (en) * 1981-12-15 1985-06-11 Jeffery Schlom Process for producing monoclonal antibodies reactive with human breast cancer
US4753894A (en) * 1984-02-08 1988-06-28 Cetus Corporation Monoclonal anti-human breast cancer antibodies

Also Published As

Publication number Publication date
JPH03503120A (ja) 1991-07-18
ES2012997A6 (es) 1990-04-16
AU3049189A (en) 1989-08-25
EP0401247A4 (en) 1991-01-23
EP0401247A1 (en) 1990-12-12
WO1989007268A1 (en) 1989-08-10

Similar Documents

Publication Publication Date Title
Hand et al. Expression of laminin receptor in normal and carcinomatous human tissues as defined by a monoclonal antibody
Edwards et al. Monoclonal antibody identification and characterization of a M r 43,000 membrane glycoprotein associated with human breast cancer
Stacker et al. A new breast carcinoma antigen defined by a monoclonal antibody
US4894326A (en) Monoclonal antibody defining oncofetal structure of fibronectin
Abbasi et al. CD44 is associated with proliferation in normal and neoplastic human colorectal epithelial cells
CN1009055B (zh) 生产人类肿瘤相关抗原的单克隆抗体的杂交瘤细胞系的制备方法
Yoshida et al. Monoclonal antibody to a proximal nephrogenic renal antigen: immunohistochemical analysis of formalin-fixed, paraffin-embedded human renal cell carcinomas
Beauchemin et al. A mouse analogue of the human carcinoembryonic antigen
CN1036793A (zh) 人体癌细胞新型类粘性糖蛋白表面抗原的专一性单克隆抗体
Favrot et al. Expression of integrin receptors on 45 clinical neuroblastoma specimens
JP3284133B2 (ja) ヒト乳脂肪小球膜ムチン抗原の糖タンパク質を確認する単クローン性抗体
CN1296711C (zh) 乳腺癌的Her－2免疫组织化学诊断试剂盒
CN1040623A (zh) 对人癌细胞新粘蛋白样糖蛋白抗原的特异性单克隆抗体
AU682607B2 (en) Monoclonal antibody specific for vascular endothelial cell antigen endoglyx-1, the antigen itself, and uses thereof
JPH07500723A (ja) 上皮起源の腫瘍細胞及び腫瘍における分化及び侵入性の検出法及び検出用核酸プローブ
Bhattacharya et al. Identification of a human cancer-associated antigen defined with monoclonal antibody
CN106432463A (zh) 一种肿瘤特异性抗原tsp70及其应用
Ashorn et al. Use of immunohistochemical staining panel for characterisation of ovarian neoplasms.
Hosaka et al. Heterogeneous expression of S-100 protein subunits α and β in cystadenolymphomas of salivary glands
US5177000A (en) Monoclonal antibodies selective for prostate cancer and diagnostic immunoassay for prostate cancer
CN1854711A (zh) 乳腺癌的Her－2免疫组织化学诊断试剂盒检测对象的处理方法
NO903467L (no) Monoklonalt antistoff spesifikt for et nytt mucinglykoprotein-overflateantigen paa humane karcinomceller.
CA1221926A (en) Monoclonal, antibodies to cell surface antigens of human malignant melanoma
CN117946244A (zh) 一种cd73蛋白的检测方法、试剂盒及其应用
Buszello et al. Detection of endogenous receptors for carbohydrate ligands in primary and metastatic human renal cell carcinoma

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C01 Deemed withdrawal of patent application (patent law 1993)
WD01 Invention patent application deemed withdrawn after publication