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抑制细胞缺失疗法:使用血卟啉偶联单克隆抗体在体内选择性清除抑制性T细胞,可使动物排斥同基因肿瘤细胞。

Suppressor deletion therapy: selective elimination of T suppressor cells in vivo using a hematoporphyrin conjugated monoclonal antibody permits animals to reject syngeneic tumor cells.

作者信息

Steele J K, Liu D, Stammers A T, Whitney S, Levy J G

机构信息

Department of Pathology, Harvard Medical School, Boston, Massachusetts.

出版信息

Cancer Immunol Immunother. 1988;26(2):125-31. doi: 10.1007/BF00205605.

DOI:10.1007/BF00205605
PMID:2965972
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11038255/
Abstract

A MAb (B16G) which recognizes a constant epitope on TsC and their soluble factors in DBA/2 mice has been described previously. In this study, we show that when this MAb is covalently linked to the photoactivable molecule Hp, and injected i.v. into P815 tumor-bearing mice which were subsequently exposed to light, tumors undergo permanent regression in 10%-40% of these mice (depending on the individual experiment). All control animals died within an average of 22-24 days after tumor cell injection. It is suggested that tumor regression is attributable to immune mechanisms facilitated by the elimination of a population of TsC. When splenocytes of B16G-Hp-treated mice were assayed in vitro for the generation of CTL active against P815 tumor cells, it was found that 24 h after treatment, a significant increase in killer cell activity was noted but that this effect was gone by 48h. We also show that B16G-Hp conjugates are capable in vitro of specifically killing cells of a TsC hybridoma, A10 (which has been shown previously to secrete a T suppressor factor reactive with P815 cell surface antigens). This conjugate had no cytotoxic effect on P815 cells under conditions in which A10 cells were killed.

摘要

先前已报道过一种单克隆抗体(B16G),它能识别DBA/2小鼠中TsC及其可溶性因子上的一个恒定表位。在本研究中,我们发现,当这种单克隆抗体与可光活化分子Hp共价连接,并静脉注射到荷P815肿瘤的小鼠体内,随后对其进行光照时,10%-40%的小鼠(取决于个体实验)肿瘤会发生永久性消退。所有对照动物在注射肿瘤细胞后平均22-24天内死亡。提示肿瘤消退归因于TsC群体消除所促进的免疫机制。当对B16G-Hp处理小鼠的脾细胞进行体外检测,以测定针对P815肿瘤细胞的CTL生成情况时,发现处理后24小时,杀伤细胞活性显著增加,但这种效应在48小时后消失。我们还表明,B16G-Hp偶联物在体外能够特异性杀伤TsC杂交瘤A10的细胞(先前已证明该杂交瘤分泌与P815细胞表面抗原反应的T抑制因子)。在杀死A10细胞的条件下,这种偶联物对P815细胞没有细胞毒性作用。

相似文献

1
Suppressor deletion therapy: selective elimination of T suppressor cells in vivo using a hematoporphyrin conjugated monoclonal antibody permits animals to reject syngeneic tumor cells.抑制细胞缺失疗法:使用血卟啉偶联单克隆抗体在体内选择性清除抑制性T细胞,可使动物排斥同基因肿瘤细胞。
Cancer Immunol Immunother. 1988;26(2):125-31. doi: 10.1007/BF00205605.
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Suppressor deletion therapy. Selective elimination of T suppressor cells using a hematoporphyrin-conjugated monoclonal antibody.
Targeted Diagn Ther. 1988;1:157-89.
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Isolation and characterization of a tumor-specific T suppressor factor from a T cell hybridoma.从T细胞杂交瘤中分离并鉴定一种肿瘤特异性T抑制因子。
J Immunol. 1985 Apr;134(4):2767-78.
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Immunization of DBA/2 mice with a T cell hybridoma-derived TsF increases immune resistance to the syngeneic tumors P815 and L1210.用T细胞杂交瘤衍生的TsF对DBA/2小鼠进行免疫可增强对同基因肿瘤P815和L1210的免疫抵抗力。
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Failure of anti-T cell monoclonal antibodies to prevent acute tumor allograft rejection is associated with their inability to deplete or inactivate T cells at the site of rejection.抗T细胞单克隆抗体无法预防急性肿瘤同种异体移植排斥反应,这与其无法在排斥反应部位清除或使T细胞失活有关。
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[The specific photodynamic effect of monoclonal antibodies conjugated with hematoporphyrin derivative on gastric cancer in vitro and in vivo].
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A monoclonal antibody raised to tumor-specific T cell-derived suppressor factors also recognizes T suppressor inducer factors of the 4-hydroxy-3-nitrophenyl acetyl hapten suppressor network.
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Antibody-targeted polymer-bound drugs.抗体靶向的聚合物结合药物。
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Comparison of T suppressor factors from tumour-bearing mice and mice immunized with a monoclonal anti-idiotypic antibody.荷瘤小鼠与用单克隆抗独特型抗体免疫的小鼠的抑制性T因子比较。
Cancer Immunol Immunother. 1990;31(3):151-6. doi: 10.1007/BF01744729.

本文引用的文献

1
Stimulation of different pathways of T-cell functions by syngeneic tumor cells and soluble membrane proteins.同基因肿瘤细胞和可溶性膜蛋白对T细胞功能不同途径的刺激。
Cell Immunol. 1983 May;78(1):13-22. doi: 10.1016/0008-8749(83)90255-1.
2
Characterization of a monoclonal antibody directed to a T cell suppressor factor.
J Immunol. 1983 Oct;131(4):1843-8.
3
Photoimmunotherapy: treatment of animal tumors with tumor-specific monoclonal antibody-hematoporphyrin conjugates.光免疫疗法:用肿瘤特异性单克隆抗体-血卟啉偶联物治疗动物肿瘤。
J Immunol. 1983 Mar;130(3):1473-7.
4
Ability of specific monoclonal antibodies and conventional antisera conjugated to hematoporphyrin to label and kill selected cell lines subsequent to light activation.特定单克隆抗体及与血卟啉偶联的传统抗血清在光激活后标记并杀死选定细胞系的能力。
Cancer Res. 1985 Sep;45(9):4380-6.
5
Immunization of DBA/2 mice with a T cell hybridoma-derived TsF increases immune resistance to the syngeneic tumors P815 and L1210.用T细胞杂交瘤衍生的TsF对DBA/2小鼠进行免疫可增强对同基因肿瘤P815和L1210的免疫抵抗力。
J Immunol. 1986 Nov 1;137(9):3025-30.
6
The role of suppressor T cells in BCNU-mediated rejection of a syngeneic tumor.抑制性T细胞在卡氮芥介导的同基因肿瘤排斥反应中的作用。
J Immunol. 1985 Aug;135(2):1510-7.
7
Preliminary characterization of human T cell suppressor factor (HTsF) isolated from tonsil cells by monoclonal antibody immunoadsorbence.
J Immunol. 1985 Aug;135(2):1201-6.
8
Preliminary characterization of a soluble immunosuppressive molecule from DBA/2 spleen cells using monoclonal antibody immunoadsorbence.
Cell Immunol. 1985 Feb;90(2):303-13. doi: 10.1016/0008-8749(85)90195-9.
9
Isolation and characterization of a tumor-specific T suppressor factor from a T cell hybridoma.从T细胞杂交瘤中分离并鉴定一种肿瘤特异性T抑制因子。
J Immunol. 1985 Apr;134(4):2767-78.
10
In vitro induction of cytotoxicity against syngeneic mastocytoma and its suppression by spleen and thymus cells from tumor-bearing mice.体外诱导对同基因肥大细胞瘤的细胞毒性及其被荷瘤小鼠的脾细胞和胸腺细胞抑制的情况。
J Immunol. 1976 Feb;116(2):288-93.