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新型免疫增强剂N-(4-[(4-氟苯基)磺酰基]苯基)乙酰胺(CL 259, 763)对小鼠细胞毒性T淋巴细胞反应的恢复作用

Restoration of cytolytic T-lymphocyte response with a new immunopotentiator, N-(4-[(4-fluorophenyl)sulfonyl]phenyl)acetamide (CL 259, 763), in mice.

作者信息

Wang B S, Ruszala-Mallon V M, Lumanglas A L, Silva J, Durr F E

机构信息

Chemotherapy Research Department, American Cyanamid Company, Lederle Laboratories, Pearl River, New York 10965.

出版信息

Cancer Res. 1988 Apr 15;48(8):2135-7.

PMID:3258185
Abstract

The immunorestorative characteristics of a novel synthetic immunomodulator, N-(4-[(4-fluorophenyl)sulfonyl]phenyl)acetamide (CL 259, 763), has been investigated in several experimental models. In one situation, the compound was shown to enhance the induction of a cytolytic T-lymphocyte response to the murine MBL-2 leukemia implanted in its syngeneic host in which only a minimal reactivity to the tumor is normally displayed. In a Vaccinia virus model, the compound similarly augmented the lytic activity of cytolytic T-lymphocyte to virus-infected targets in not only viral antigen-primed but also cyclosporin A-impaired mice. Likewise, the alloreactive cytolytic T-lymphocyte activity was recovered in animals immunocompromised by inoculation with murine plasmacytomas or cytoreductive anticancer drugs, such as cyclophosphamide and 5-fluorouracil. Thus, the present findings suggest that CL 259,763 is effective in potentiating the immune response to weak antigens as well as in restoring alloreactivity by sparing the immunotoxicity associated with the administration of cytotoxic drugs and the growth of neoplasms.

摘要

一种新型合成免疫调节剂N-(4-[(4-氟苯基)磺酰基]苯基)乙酰胺(CL 259,763)的免疫恢复特性已在多个实验模型中进行了研究。在一种情况下,该化合物被证明可增强对植入同基因宿主的鼠MBL-2白血病的细胞毒性T淋巴细胞反应的诱导,在该宿主中通常仅显示对肿瘤的最小反应性。在痘苗病毒模型中,该化合物不仅在病毒抗原致敏的小鼠中,而且在环孢菌素A受损的小鼠中,同样增强了细胞毒性T淋巴细胞对病毒感染靶标的裂解活性。同样,在通过接种鼠浆细胞瘤或细胞减灭性抗癌药物(如环磷酰胺和5-氟尿嘧啶)而免疫受损的动物中,同种异体反应性细胞毒性T淋巴细胞活性得以恢复。因此,目前的研究结果表明,CL 259,763可有效增强对弱抗原的免疫反应,并通过避免与细胞毒性药物给药和肿瘤生长相关的免疫毒性来恢复同种异体反应性。

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