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一种用于生产人单克隆抗体的人杂交骨髓瘤。

A human hybrid myeloma for production of human monoclonal antibodies.

作者信息

Kozbor D, Tripputi P, Roder J C, Croce C M

出版信息

J Immunol. 1984 Dec;133(6):3001-5.

PMID:6092464
Abstract

We produced somatic cell hybrids between human myeloma cells and a lymphoblastoid cell line that is hypoxanthine phosphoribosyl transferase-deficient and ouabain-resistant. These hybrids were phenotypically similar to the human myeloma parental cells and grew as well as the human lymphoblastoid parental cells. After counterselection in 6-thioguanine, mutants that were 6-thioguanine-and ouabain-resistant were obtained, one of which was used as a fusion partner with lymphoblastoid B cells that produce anti-tetanus toxoid (TT) antibodies. These hybrids secreted human anti-TT monoclonal antibodies in much larger amounts than the parental lymphoblastoid cells, and were stable for a period of over 10 mo until the present time. Thus, by hybridizing plasmacytomas with lymphoblastoid cells, we constructed a fusion partner that secretes large amounts of immunoglobulin (Ig), grows at a fast rate, has a high fusion frequency, and supports the production of monoclonal antibodies over long periods of time. Moreover, anti-TT antibody-producing hybrids have been grown as solid tumors in irradiated BALB/c nude mice and then adopted to ascites growth, producing 1 to 8 mg of human immunoglobulin per 1 ml of ascites fluid.

摘要

我们制备了人骨髓瘤细胞与一种次黄嘌呤磷酸核糖基转移酶缺陷且对哇巴因耐药的淋巴母细胞系之间的体细胞杂种。这些杂种在表型上与亲本骨髓瘤细胞相似,生长情况与亲本淋巴母细胞一样良好。在6-硫鸟嘌呤中进行反选择后,获得了对6-硫鸟嘌呤和哇巴因耐药的突变体,其中一个被用作与产生抗破伤风类毒素(TT)抗体的淋巴母细胞B细胞的融合伙伴。这些杂种分泌的人抗TT单克隆抗体比亲本淋巴母细胞多得多,并且直到现在在超过10个月的时间内都保持稳定。因此,通过将浆细胞瘤与淋巴母细胞杂交,我们构建了一个能分泌大量免疫球蛋白(Ig)、生长迅速、融合频率高且能长期支持单克隆抗体产生的融合伙伴。此外,产生抗TT抗体的杂种已在经辐照的BALB/c裸鼠中长成实体瘤,然后转为腹水生长,每1毫升腹水中产生1至8毫克人免疫球蛋白。

相似文献

1
A human hybrid myeloma for production of human monoclonal antibodies.一种用于生产人单克隆抗体的人杂交骨髓瘤。
J Immunol. 1984 Dec;133(6):3001-5.
2
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引用本文的文献

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Use of Human Hybridoma Technology To Isolate Human Monoclonal Antibodies.利用人杂交瘤技术分离人单克隆抗体。
Microbiol Spectr. 2015 Feb;3(1):AID-0027-2014. doi: 10.1128/microbiolspec.AID-0027-2014.
2
Development of human monoclonal antibodies: A review.人源化单克隆抗体的开发:综述。
Cytotechnology. 1996 Jan;21(3):183-93. doi: 10.1007/BF00365341.
3
Preclinical in vitro and in vivo characterization of the fully human monoclonal IgM antibody KBPA101 specific for Pseudomonas aeruginosa serotype IATS-O11.针对铜绿假单胞菌血清型 IATS-O11 的全人源单克隆 IgM 抗体 KBPA101 的临床前体外和体内特性研究。
Antimicrob Agents Chemother. 2010 Jun;54(6):2338-44. doi: 10.1128/AAC.01142-09. Epub 2010 Mar 22.
4
An optimized electrofusion-based protocol for generating virus-specific human monoclonal antibodies.一种用于生成病毒特异性人单克隆抗体的基于电融合的优化方案。
J Immunol Methods. 2008 Jul 31;336(2):142-51. doi: 10.1016/j.jim.2008.04.008. Epub 2008 May 5.
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A study of human-human hybridomas from patients with autoimmune thyroid disease.对自身免疫性甲状腺疾病患者的人-人杂交瘤的研究。
J Clin Immunol. 1987 Jan;7(1):71-7. doi: 10.1007/BF00915428.
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Antibody-mediated targeting in the treatment and diagnosis of cancer: an overview.抗体介导的靶向作用在癌症治疗与诊断中的概述
Cancer Chemother Pharmacol. 1986;17(3):197-208. doi: 10.1007/BF00256685.
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Establishment of a human monoclonal antibody to Hanganutziu-Deicher antigen as a tumor-associated carbohydrate antigen.建立一种针对汉努齐乌-戴歇尔抗原(一种肿瘤相关碳水化合物抗原)的人单克隆抗体。
Jpn J Cancer Res. 1988 Dec;79(12):1340-8. doi: 10.1111/j.1349-7006.1988.tb01565.x.