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使用单克隆抗体17-1A的抗体依赖性细胞毒性(ADCC)中的淋巴因子激活杀伤(LAK)细胞:一种在肿瘤治疗中可能有用的组合。

Lymphokine activated killer (LAK) cells in antibody dependent cellular cytotoxicity (ADCC) using MAb 17-1A: a combination of potential usefulness in tumor therapy.

作者信息

Masucci G, Wersäll P, Nielsen J, Nielsen H K, Wigzell H, Mellstedt H

机构信息

Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.

出版信息

Hybridoma. 1989 Oct;8(5):507-16. doi: 10.1089/hyb.1989.8.507.

DOI:10.1089/hyb.1989.8.507
PMID:2807310
Abstract

Peripheral blood lymphocytes (PBL) stimulated by interleukin-2 (IL-2) for 48-96h, generated killer cells against the human colon cancer cell line SW948. The killing capacity increased significantly when the specific mouse monoclonal antibody (MAb) 17-1A was present during the lytic process. The chimeric antibody 17-1A determined a significantly stronger cytotoxicity compared to mouse MAb 17-1A. MAb BR55-2 which recognizes a different antigen on SW948 target cells mediated a similar cytotoxicity as MAb 17-1A. Presence of alpha-interferon (IFN) during the lytic assay significantly enhanced the killing of the tumor by lymphokine activated killer (LAK) cells as well as by LAK cells and mouse MAb 17-1A. However, when chimeric MAb 17-1A and LAK cells were used alpha-IFN failed to increase the lytic activity, probably due to already maximum lysis in the system. Combinations of various biological response modifiers such as monoclonal antibodies, IL-2/LAK cells and alpha-IFN carry great promise to improve this kind of therapy for cancer patients.

摘要

外周血淋巴细胞(PBL)在白细胞介素-2(IL-2)刺激下培养48 - 96小时后,可产生针对人结肠癌细胞系SW948的杀伤细胞。在裂解过程中存在特异性小鼠单克隆抗体(MAb)17-1A时,杀伤能力显著增强。与小鼠MAb 17-1A相比,嵌合抗体17-1A具有显著更强的细胞毒性。识别SW948靶细胞上不同抗原的MAb BR55-2介导的细胞毒性与MAb 17-1A相似。在裂解试验中,α-干扰素(IFN)的存在显著增强了淋巴因子激活的杀伤细胞(LAK)以及LAK细胞和小鼠MAb 17-1A对肿瘤的杀伤作用。然而,当使用嵌合MAb 17-1A和LAK细胞时,α-干扰素未能增加裂解活性,这可能是由于系统中已达到最大裂解程度。各种生物反应调节剂如单克隆抗体、IL-2/LAK细胞和α-干扰素的联合应用有望极大地改善对癌症患者的此类治疗。

相似文献

1
Lymphokine activated killer (LAK) cells in antibody dependent cellular cytotoxicity (ADCC) using MAb 17-1A: a combination of potential usefulness in tumor therapy.使用单克隆抗体17-1A的抗体依赖性细胞毒性(ADCC)中的淋巴因子激活杀伤(LAK)细胞:一种在肿瘤治疗中可能有用的组合。
Hybridoma. 1989 Oct;8(5):507-16. doi: 10.1089/hyb.1989.8.507.
2
Effect of human blood mononuclear cell populations in antibody dependent cellular cytotoxicity (ADCC) using two murine (CO17-1A and Br55-2) and one chimeric (17-1A) monoclonal antibodies against a human colorectal carcinoma cell line (SW948).使用两种抗人结肠癌细胞系(SW948)的鼠源单克隆抗体(CO17 - 1A和Br55 - 2)以及一种嵌合单克隆抗体(17 - 1A),研究人血单核细胞群体在抗体依赖性细胞毒性(ADCC)中的作用。
Hybridoma. 1988 Oct;7(5):429-40. doi: 10.1089/hyb.1988.7.429.
3
Combined therapy of mice bearing a lymphokine-activated killer-resistant tumor with recombinant interleukin 2 and an antitumor monoclonal antibody capable of inducing antibody-dependent cellular cytotoxicity.用重组白细胞介素2和一种能够诱导抗体依赖性细胞毒性的抗肿瘤单克隆抗体对携带抗淋巴因子激活的杀伤细胞肿瘤的小鼠进行联合治疗。
Cancer Res. 1988 Mar 1;48(5):1173-9.
4
Lymphokine-activated killer cell cytotoxicity against human colon carcinomas enhanced by monoclonal antibody D612.单克隆抗体D612增强淋巴因子激活的杀伤细胞对人结肠癌的细胞毒性。
Int J Cancer. 1990 Dec 15;46(6):1021-8. doi: 10.1002/ijc.2910460613.
5
Chimeric B72.3 mouse/human (IgG1) antibody directs the lysis of tumor cells by lymphokine-activated killer cells.嵌合的B72.3小鼠/人(IgG1)抗体可引导淋巴因子激活的杀伤细胞对肿瘤细胞进行裂解。
Cancer Immunol Immunother. 1990;31(6):349-57. doi: 10.1007/BF01741406.
6
Tumor growth suppression by a mouse/human chimeric anti-CEA antibody and lymphokine-activated killer cells in vitro and in SCID mouse xenograft model.小鼠/人嵌合抗癌胚抗原抗体及淋巴因子激活的杀伤细胞在体外和SCID小鼠异种移植模型中对肿瘤生长的抑制作用
Anticancer Res. 1998 Jan-Feb;18(1A):17-24.
7
Combinations of the cytokines IL-12, IL-2 and IFN-alpha significantly augment whereas the cytokine IL-4 suppresses the cytokine-induced antibody-dependent cellular cytotoxicity of monoclonal antibodies 17-1A and BR55-2.细胞因子白细胞介素-12、白细胞介素-2和干扰素-α的组合显著增强,而细胞因子白细胞介素-4则抑制细胞因子诱导的单克隆抗体17-1A和BR55-2的抗体依赖性细胞毒性。
Cytokine. 2000 Jun;12(6):756-61. doi: 10.1006/cyto.1999.0610.
8
Differential modulation of LAK and ADCC functions of natural killer cells from AK-5 tumor-bearing rats by IL-2, IL-12 and IFN-gamma.IL-2、IL-12和IFN-γ对AK-5荷瘤大鼠自然杀伤细胞LAK和ADCC功能的差异调节
Cytokines Cell Mol Ther. 1997 Mar;3(1):51-8.
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Enhanced cytotoxicity against colon carcinoma by combinations of noncompeting monoclonal antibodies to the 17-1A antigen.针对17-1A抗原的非竞争性单克隆抗体组合增强对结肠癌的细胞毒性作用。
Cancer Res. 1988 Nov 15;48(22):6303-8.
10
IL-4 regulation of murine lymphokine-activated killer activity in vitro. Effects on the IL-2-induced expansion, cytotoxicity, and phenotype of lymphokine-activated killer effectors.白细胞介素-4对小鼠淋巴细胞激活的杀伤活性的体外调节。对白细胞介素-2诱导的淋巴细胞激活的杀伤效应细胞的扩增、细胞毒性及表型的影响。
J Immunol. 1989 Jan 15;142(2):726-33.

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In vitro and in vivo pharmacology and pharmacokinetics of a human engineered monoclonal antibody to epithelial cell adhesion molecule.一种针对上皮细胞粘附分子的人源化工程单克隆抗体的体外和体内药理学及药代动力学
Neoplasia. 2003 Mar-Apr;5(2):146-54. doi: 10.1016/s1476-5586(03)80006-4.
2
Granulocyte-monocyte colony-stimulating-factor augments the interleukin-2-induced cytotoxic activity of human lymphocytes in the absence and presence of mouse or chimeric monoclonal antibodies (mAb 17-1A).在不存在和存在小鼠或嵌合单克隆抗体(mAb 17-1A)的情况下,粒细胞-单核细胞集落刺激因子增强白细胞介素-2诱导的人淋巴细胞的细胞毒性活性。
Cancer Immunol Immunother. 1990;31(4):231-5. doi: 10.1007/BF01789174.
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Chemotherapy and immunotherapy of colorectal cancer.
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