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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.

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。

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