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两种小鼠B细胞淋巴瘤的双特异性抗体治疗

Bispecific antibody therapy of two murine B-cell lymphomas.

作者信息

Demanet C, Brissinck J, Moser M, Leo O, Thielemans K

机构信息

Unit of Hematology-Immunology, Vrije Universiteit Brussel (VUB), Belgium.

出版信息

Int J Cancer Suppl. 1992;7:67-8.

PMID:1428409
Abstract

Numerous in vitro studies have shown that T lymphocytes can be targeted towards any target cell by using bispecific antibodies (bsAbs) with specificity of the CD3/TCR complex and a target cell antigen. We have produced bsAbs directed against the membrane expressed idiotype of the murine B cell lymphomas BCLI and 38C13, and murine CD3 complex. The dual specificity of the hybrid-hybridoma produced monoclonal antibodies (MAbs) could be demonstrated by flow cytometry, the induction of T cell proliferation, the induction of IL2 secretion by polyclonal T cells, and redirected lysis of the relevant target cells. Immunotherapy of tumor bearing animals demonstrated that bsAbs could efficiently target T cells towards the tumor cells, that tumor cell--T cell bridging is established in vivo, and that both T cell subsets contribute to tumor regression resulting in long-term survival and cure of the lymphomas.

摘要

众多体外研究表明,通过使用对CD3/TCR复合物和靶细胞抗原具有特异性的双特异性抗体(bsAb),T淋巴细胞可靶向任何靶细胞。我们制备了针对小鼠B细胞淋巴瘤BCLI和38C13的膜表达独特型以及小鼠CD3复合物的双特异性抗体。通过流式细胞术、T细胞增殖的诱导、多克隆T细胞IL2分泌的诱导以及相关靶细胞的重定向裂解,可证明杂交 - 杂交瘤产生的单克隆抗体(mAb)的双重特异性。荷瘤动物的免疫治疗表明,双特异性抗体可有效地将T细胞靶向肿瘤细胞,在体内建立肿瘤细胞 - T细胞桥接,并且两个T细胞亚群均有助于肿瘤消退,从而导致淋巴瘤的长期存活和治愈。

相似文献

1
Bispecific antibody therapy of two murine B-cell lymphomas.两种小鼠B细胞淋巴瘤的双特异性抗体治疗
Int J Cancer Suppl. 1992;7:67-8.
2
Immunotherapy with bispecific antibodies.双特异性抗体免疫疗法。
Verh K Acad Geneeskd Belg. 1995;57(3):229-47; discussion 247-8.
3
Treatment of murine B cell lymphoma with bispecific monoclonal antibodies (anti-idiotype x anti-CD3).用双特异性单克隆抗体(抗独特型x抗CD3)治疗小鼠B细胞淋巴瘤。
J Immunol. 1991 Aug 1;147(3):1091-7.
4
Role of T-cell subsets in the bispecific antibody (anti-idiotype x anti-CD3) treatment of the BCL1 lymphoma.T细胞亚群在双特异性抗体(抗独特型x抗CD3)治疗BCL1淋巴瘤中的作用。
Cancer Res. 1994 Jun 1;54(11):2973-8.
5
Bispecific anti-idiotype/anti-CD3 antibody therapy of murine B cell lymphoma.鼠源B细胞淋巴瘤的双特异性抗独特型/抗CD3抗体疗法。
J Immunol. 1991 Dec 1;147(11):4035-44.
6
Treatment of mice bearing BCL1 lymphoma with bispecific antibodies.用双特异性抗体治疗携带BCL1淋巴瘤的小鼠。
J Immunol. 1991 Dec 1;147(11):4019-26.
7
Idiotype vaccination strategies against a murine B-cell lymphoma: dendritic cells loaded with idiotype and bispecific idiotype x anti-class II antibodies can protect against tumor growth.针对小鼠B细胞淋巴瘤的独特型疫苗接种策略:负载独特型以及双特异性独特型x抗II类抗体的树突状细胞可预防肿瘤生长。
Cytokines Mol Ther. 1996 Dec;2(4):231-8.
8
The role of T cell activation in anti-CD3 x antitumor bispecific antibody therapy.T细胞活化在抗CD3×抗肿瘤双特异性抗体治疗中的作用。
J Immunol. 1994 Mar 1;152(5):2385-92.
9
Bispecific IgG and IL-2 therapy of a syngeneic B-cell lymphoma in immunocompetent mice.在免疫活性小鼠中对同基因B细胞淋巴瘤进行双特异性IgG和白细胞介素-2治疗。
Int J Cancer Suppl. 1992;7:63-6.
10
Visualization of effective tumor targeting by CD8+ natural killer T cells redirected with bispecific antibody F(ab')(2)HER2xCD3.用双特异性抗体F(ab')(2)HER2xCD3重定向的CD8+自然杀伤T细胞对有效肿瘤靶向的可视化
Cancer Res. 2002 Oct 15;62(20):5785-91.

引用本文的文献

1
Development of a novel bi-specific monoclonal antibody approach for tumour targeting.一种用于肿瘤靶向的新型双特异性单克隆抗体方法的研发。
Br J Cancer. 1999 Oct;81(3):431-9. doi: 10.1038/sj.bjc.6690712.
2
Targeting of peripheral blood T lymphocytes.外周血T淋巴细胞的靶向作用。
Springer Semin Immunopathol. 1996;18(2):211-26. doi: 10.1007/BF00820667.