CN1205012A - 泌尿生殖癌tlp复合体肽及其抗体 - Google Patents

泌尿生殖癌tlp复合体肽及其抗体 Download PDF

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CN1205012A
CN1205012A CN97191213A CN97191213A CN1205012A CN 1205012 A CN1205012 A CN 1205012A CN 97191213 A CN97191213 A CN 97191213A CN 97191213 A CN97191213 A CN 97191213A CN 1205012 A CN1205012 A CN 1205012A
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tlp
peptide
urogenital
antibody
amino acid
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CN1136230C (zh
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朱利奥·塔若
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Istituto Farmaceoterapico Italiano S P A
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4748—Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

本文描述了含有特异泌尿生殖癌TLP表位的肽,其中TLP包含氨基酸序列:Gly Pro Pro Glu Val Gln Asn AlaAsn。另外也描述了检测所述泌尿生殖TLPs的试剂及药物组合物。

Description

泌尿生殖癌TLP复合体肽及其抗体
本发明涉及从泌尿生殖器癌中分离出来的TLP复合体(肿瘤释放蛋白)的肽。
具体地讲，本发明涉及来自人泌尿生殖器的具有抗原活性的TLP蛋白复合体的肽，以及能与所述肽反应的抗体，所述抗体可用于诊断及临床。
TLP复合体是存在于人肿瘤细胞中的蛋白复合体。有人描述了一种214KDa的TLP蛋白(Tarro G．，Oncology 40，248-253，1983)。可用欧洲专利283443中所描述的方法来从肿瘤组织中分离TLP。意大利专利申请RM92A000506从肺癌中识别了一种TLP蛋白。本发明的发明人惊奇地发现来自泌尿生殖器癌的TLP含有新肽，这些新肽含有不同于已知TLP肽的序列。
因此，需要从泌尿生殖癌中鉴别出起表位作用的TLP肽，以制备作为抗体的特异试剂。
本发明的发明人已识别出具有一定序列的肽，所述序列包含于来自子宫颈或睾丸腺癌、以及肾瘤的214KDa的TLP蛋白的序列中。
因此本发明的一个目的是提供含有特异性泌尿生殖癌TLP表位的肽，其中所述的TLP的特征是含有SEQ ID No．1的氨基酸序列：
Gly Pro Pro Glu Val Gln Asn Ala Asn
按照优选实施方案，其中的肽含有SEQ ID No．1的氨基酸序列。
本发明的再一目的是提供能从泌尿生殖癌中识别TLP的特异性试剂，所述试剂优选含有TLP抗体。更优选地，所述抗体可识别具有SEQID No．1序列的肽片断。
本发明的又一目的是提供诊断试剂盒，所述试剂盒含有本发明抗体作为特异性试剂，以从样品中识别TLP。
本发明的另一目的是提供含有本发明肽作为活性剂的药物组合物。
现在用说明性并非限制性的实例对本发明进行描述。实施例1  肿瘤浸出液的制备
将来自一患有子宫癌的45岁妇女的12．55g的肿瘤在室温下解冻，并且用外科方法除去坏死组织。当将所得到的物质匀化后，用Tris 1×(10mM Tris-HCl，pH7．2)进行多次洗涤，并且将该组织进行三轮冷冻-解冻循环。
收集使用过的Tris洗涤液并在33，000rpm下离心1小时。收集上清液并进行冷冻。
将组织用声波处理三次达3分钟，随后在33，000rpm下超离心120分钟。收集上清液(5．7ml)，在Agrodisc过滤器(0．45μm)上过滤，并将过滤后得的组织悬浮在Tris溶液中，比例为1g／ml Tris，并将其在33，000rpm下超离心60分钟。过滤上清液(0．5ml)并将其加入上一次的上清液中。
对睾丸癌(总产量1．9ml)及肾瘤样品进行同样的处理。实施例2  对来自泌尿生殖器癌的TLP蛋白中包含的肽的识别
如欧洲专利283443中所述，将TLP复合物从泌尿生殖器癌浸出液中分离出来。所使用的样品是：
1)子宫颈腺癌；
2)睾丸癌；
3)肾瘤。
所得到的蛋白含量如下：
　　　　　　　　　　　表1
样品          总mg数      mg／ml TLP
子宫颈腺癌     59．5        9．6
睾丸癌          7．4        3．9
肾瘤            7．4*       1．5
*总肾蛋白浓度不允许足够的TLP纯化产量。
用变性电泳分析方法(SDS)，通过分子量测定(214KDa)来进行TLP识别。
通过取下相应于表观分子量214kDa的凝胶部分并进一步用电洗脱仪(AMICON)进行电洗脱以去除大部分的污染物。
随后通过变性电泳分析确定TLP的纯度。然后将TLP移至具有很高的蛋白质结合能力的PVDF(聚二氟乙烯(Polyvinylidifluoride))膜上，再用Applied Biosystems的蛋白质自动测序仪按照Edman方法进行氨基酸序列分析。
在所有样品中发现的氨基酸序列如下：
Gly Pro Pro Glu Val Gln Asn Ala Asn(SEQ ID No．1)
　　　　　　　　　　　　序列表(1)一般信息(i)申请人
(A)名称：Istituto Farmacoterapico Italiano S．p．A．
(B)街道：Via Paolo Frisi 21／23
(C)城市：罗马
(E)国家：意大利
(F)邮政编码(ZIP)：00197
(A)名称：Tarro Giulio c／o Istituto Farmacoterapica Italiano
　　　　S．p．A．
(B)街道：Via Paolo Frisi 21／23
(C)城市：罗马
(E)国家：意大利
(F)邮政编码(ZIP)：00197
(ii)发明名称：泌尿生殖癌TLP复合体肽及其抗体
(iii)序列数：1
(iv)计算机可读形式：
(A)媒体类型：软盘
(B)计算机：IBM PC兼容机
(C)操作系统：PC-DOS／MS-DOS
(D)软件：Patentin Release#1．0，Version#1．30(EPO)(2)SEQ ID NO：1的信息：(i)序列特征：
(A)长度：9个氨基酸
(B)类型：氨基酸
(C)链型：单链
(D)拓朴学：线性
(ii)分子类型：肽
(xi)序列描述：SEQ ID NO：1：
　　Gly Pro Pro Glu Val Gln Asn Ala Asn
　　 1               5

Claims (6)

1．包含TLP泌尿生殖特异性表位的肽，其中所述TLP包含SEQ IDNo．1的氨基酸序列。
2．根据权利要求1的肽，该肽包含SEQ ID No．1的氨基酸序列。
3．可识别至少一种根据权利要求1或2的肽的抗体。
4．从泌尿生殖肿瘤样品中识别TLP的诊断试剂盒，所述试剂盒包含根据权利要求3的作为特异试剂的抗体。
5．从泌尿生殖肿瘤样品中识别TLP复合体的方法，其特征在于包含以下步骤：
-用第一份抗权利要求1或2的肽的免疫血清对所述样品进行免疫沉淀；
-通过与第二份所述免疫血清进行反应以及用所述反应的检测方法来从第一免疫沉淀物中检测所述TLP复合体。
6．含有权利要求1的肽作为活性剂的药物组合物。
CNB971912130A 1996-07-10 1997-07-02 泌尿生殖癌tlp复合体肽及其抗体 Expired - Fee Related CN1136230C (zh)

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IT96RM000496A IT1284870B1 (it) 1996-07-10 1996-07-10 Peptidi dei complessi tlp da carcinomi dell'apparato urogenitale e anticorpi diretti contro di essi
ITRM96A000496 1996-07-10

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CN1205012A true CN1205012A (zh) 1999-01-13
CN1136230C CN1136230C (zh) 2004-01-28

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US (3) US6222010B1 (zh)
EP (1) EP0851872B1 (zh)
CN (1) CN1136230C (zh)
AT (1) ATE200678T1 (zh)
AU (1) AU716721B2 (zh)
CA (1) CA2234151C (zh)
DE (1) DE69704606T2 (zh)
DK (1) DK0851872T3 (zh)
ES (1) ES2156393T3 (zh)
GR (1) GR3036057T3 (zh)
IT (1) IT1284870B1 (zh)
NO (1) NO982227D0 (zh)
PT (1) PT851872E (zh)
RU (1) RU2203679C2 (zh)
SK (1) SK47098A3 (zh)
WO (1) WO1998001462A2 (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101712946A (zh) * 2009-09-27 2010-05-26 南通大学附属医院 构建生殖结节器官培养尿道体外发育模型的方法

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1284870B1 (it) 1996-07-10 1998-05-22 Ist Farmacoterapico It Spa Peptidi dei complessi tlp da carcinomi dell'apparato urogenitale e anticorpi diretti contro di essi
DE10001717C1 (de) * 2000-01-18 2001-04-26 Xcellsis Gmbh Brennstoffzellensystem
ITMI20011380A1 (it) * 2001-06-29 2002-12-29 Unihart Corp Antigene tlp e sue applicazioni diagnostiche

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4270924A (en) * 1979-04-10 1981-06-02 Crooke Stanley T Diagnostic method for detecting cancer
IT1206250B (it) 1987-02-18 1989-04-14 Ist Farmacoterapico It Spa Stiche umane e relativi prodotti metodo per l'estrazione di antigeni di membrana aventi proprieta' immunogene a partire da cellule neopla-
RU2009500C1 (ru) * 1987-03-11 1994-03-15 Фармиталиа Карло Эрба С.Р.Л. Способ получения цитотоксического коньюгата
IT1262954B (it) 1992-07-03 1996-07-23 Ist Farmacoterapico It Spa Regioni antigeniche dei complessi tpl e anticorpi diretti contro di essi.
IT1284870B1 (it) 1996-07-10 1998-05-22 Ist Farmacoterapico It Spa Peptidi dei complessi tlp da carcinomi dell'apparato urogenitale e anticorpi diretti contro di essi

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101712946A (zh) * 2009-09-27 2010-05-26 南通大学附属医院 构建生殖结节器官培养尿道体外发育模型的方法

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CA2234151C (en) 2004-02-03
EP0851872B1 (en) 2001-04-18
CN1136230C (zh) 2004-01-28
ITRM960496A1 (it) 1998-01-10
DK0851872T3 (da) 2001-06-18
AU716721B2 (en) 2000-03-02
ES2156393T3 (es) 2001-06-16
CA2234151A1 (en) 1998-01-15
IT1284870B1 (it) 1998-05-22
AU3557297A (en) 1998-02-02
EP0851872A3 (en) 1998-10-14
US6664378B1 (en) 2003-12-16
RU2203679C2 (ru) 2003-05-10
EP0851872A2 (en) 1998-07-08
ATE200678T1 (de) 2001-05-15
NO982227L (no) 1998-05-15
WO1998001462A3 (en) 1998-08-06
GR3036057T3 (en) 2001-09-28
ITRM960496A0 (zh) 1996-07-10
PT851872E (pt) 2001-08-30
SK47098A3 (en) 1999-02-11
DE69704606T2 (de) 2001-11-08
NO982227D0 (no) 1998-05-15
US20030170750A1 (en) 2003-09-11
DE69704606D1 (de) 2001-05-23
US6222010B1 (en) 2001-04-24
WO1998001462A2 (en) 1998-01-15

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