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转染卡介苗热休克蛋白 70 基因增强鼠淋巴细胞白血病细胞的免疫原性。

Enhancement of immunogenicity of murine lymphocytic leukemia cells by transfection with BCG heat shock protein 70 gene.

机构信息

The Affiliated Hospital of Medical College, Qingdao University, Shandong, China.

出版信息

Int Immunopharmacol. 2013 Jan;15(1):1-5. doi: 10.1016/j.intimp.2012.11.010. Epub 2012 Nov 24.

Abstract

The effects of BCG heat shock protein 70 (BCG HSP70) gene transfection on tumorigenicity and immunogenicity of murine lymphocytic leukemia cell line (L1210) were studied. After HSP70 gene transfection, the tumor cells became strongly immunogenic and lost their tumorigenicity in syngeneic mice. It mainly exhibited that tumor growth was slow or without the formation of tumor, mean survival time of mice was significantly prolonged and a marked stimulating effect on L1210 specific Th1 cells detected by IFN-γ ELISPOT assay. Tumor-bearing mice treated with the L1210-HSP70 cells showed thorough coagulation necrosis and abundant CD8+ T lymphocyte infiltration. Meanwhile, as the tumor vaccine, the HSP70-transfected tumor cells could induce a protective immune response in vivo. It showed that the tumor growth was significantly inhibited, tumor diameter was markedly reduced and the survival time of tumor-bearing mice was further prolonged. Immunization with it also resulted in regression of the established L1210 tumor and prolonged survival time of mice. These results suggest that gene transfection of BCG HSP70 could effectively improve the immunogenicity of tumor cells and it may be used as a suitable candidate gene-modified cell vaccine for cancer immunotherapy.

摘要

研究了卡介苗热休克蛋白 70(BCG HSP70)基因转染对小鼠淋巴细胞白血病细胞系(L1210)致瘤性和免疫原性的影响。HSP70 基因转染后,肿瘤细胞变得具有强烈的免疫原性,并在同基因小鼠中失去致瘤性。主要表现为肿瘤生长缓慢或无肿瘤形成,小鼠的平均存活时间显著延长,通过 IFN-γ ELISPOT 检测到对 L1210 特异性 Th1 细胞的显著刺激作用。用 L1210-HSP70 细胞治疗的荷瘤小鼠表现出完全的凝固性坏死和丰富的 CD8+T 淋巴细胞浸润。同时,作为肿瘤疫苗,转染 HSP70 的肿瘤细胞可在体内诱导保护性免疫应答。结果表明,肿瘤生长明显受到抑制,肿瘤直径明显减小,荷瘤小鼠的存活时间进一步延长。用它进行免疫接种还导致已建立的 L1210 肿瘤的消退和小鼠存活时间的延长。这些结果表明,BCG HSP70 的基因转染可有效提高肿瘤细胞的免疫原性,它可能被用作癌症免疫治疗的合适候选基因修饰细胞疫苗。

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