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一种突变型葡萄球菌肠毒素C2的抗肿瘤活性和免疫原性

Anti-tumor activity and immunogenicity of a mutated staphylococcal enterotoxin C2.

作者信息

Zhang J, Cai Y M, Xu M K, Song Z H, Li C Y, Wang H R, Dai H H, Zhang Z P, Liu C X

机构信息

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, PR China.

出版信息

Pharmazie. 2013 May;68(5):359-64.

Abstract

In this study, a novel SEC2 mutant with lower toxic activity, named 2M-118 (H118A/T20L/G22E), was engineered by site-directed mutagenesis of structural domains that are responsible for MHC class II molecule binding and TCR binding, respectively. Stimulating activity on murine splenocytes, anti-tumor effect and immunogenicity of 2M-118 were investigated in BALB/c mice. 2M-118 not only remained splenocyte stimulation activity, but also effectively inhibited the growth of S180 sarcoma in the BALB/c mice. Even though antibodies to 2M-118 could be induced after repeated administration, the action of 2M-118 was hardly neutralized or cross neutralized. Like other superantigens, immunosuppression could happen when 2M-118 was given at a greater dose. In conclusion, 2M-118 is a promising anti-tumor drug candidate for its acceptable toxicity and satisfying anti-tumour efficacy.

摘要

在本研究中,通过对分别负责与II类主要组织相容性复合体(MHC)分子结合和T细胞受体(TCR)结合的结构域进行定点诱变,构建了一种具有较低毒性活性的新型SEC2突变体,命名为2M-118(H118A/T20L/G22E)。在BALB/c小鼠中研究了2M-118对小鼠脾细胞的刺激活性、抗肿瘤作用和免疫原性。2M-118不仅保留了脾细胞刺激活性,还能有效抑制BALB/c小鼠中S180肉瘤的生长。尽管重复给药后可诱导产生针对2M-118的抗体,但2M-118的作用几乎未被中和或交叉中和。与其他超抗原一样,大剂量给予2M-118时可能会发生免疫抑制。总之,2M-118因其可接受的毒性和令人满意的抗肿瘤疗效,是一种有前景的抗肿瘤药物候选物。

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