HSA基因转染小鼠EL-4淋巴瘤细胞以提高其免疫原性的研究

目的探讨ＨＳＡ提供的协同刺激信号能否增强肿瘤细胞的免疫原性。方法将ＨＳＡｃＤＮＡ导入小鼠淋巴瘤细胞ＥＬ－４中，通过含Ｇ４１８的ＲＰＭＩ１６４０培养基将表达ＨＳＡ分子的ＥＬ－４细胞（ＨＳＡ＋ＥＬ－４）筛选出来。用混合淋巴细胞肿瘤细胞培养（ＭＬＴＣ）的方法观察ＨＳＡ＋ＥＬ－４细胞免疫小鼠脾细胞的增殖应答反应和ＣＴＬ杀伤活性。Ｃ５７ＢＬ／６小鼠接种野生型ＥＬ－４细胞后７ｄ，给予灭活的ＨＳＡ＋ＥＬ－４细胞瘤苗或联合低剂量ＩＬ－２治疗，观察荷瘤小鼠皮下肿瘤生长及存活期情况。结果ＨＳＡ＋ＥＬ－４细胞免疫小鼠的细胞对ＨＳＡ＋ＥＬ－４或ＥＬ－４瘤细胞刺激增殖反应及对亲本瘤细胞ＥＬ－４的杀瘤活性明显高于ＥＬ－４ｖ细胞（空载体转染的ＥＬ－４细胞）免疫小鼠脾细胞的。ＨＳＡ＋ＥＬ－４细胞作为瘤苗，早期治疗荷瘤小鼠，可延缓肿瘤的生长，延长荷瘤小鼠的存活期，尤其与低剂量ＩＬ－２联合应用时治疗效果更好。结论协同刺激分子ＨＳＡ在肿瘤细胞上的表达可增强瘤细胞的免疫原性；表达ＨＳＡ分子的肿瘤细胞可在小鼠体内诱导出有效的抗肿瘤免疫应答反应。

Study on Restoration of Tumor Cell Immunogenicity by Transfecting HSA Gene into Murine Lymphoma Cell Line EL4

Purpose To examine whether the co stimulatory signal provided by HSA can restore tumor cell immunogenicity. Methods HSA cDNA was transfected into the murine lymphoma cell line EL4,EL4 cells expressing HSA molecule (HSA EL4) was selected in RPMI 1640 medium containing G418.The proliferative res ponse and CTL activity of spleen cells from mice immunized with HSA EL4 cells were observed in nixed lymphocyte tumor cell culture (MLTC).C57BL/6 mice were vaccinated with inactivated HSA EL4 cells, or plus low dose of IL2 7 days after wild EL4 cell inoculation. Then, the growth of subcutaneous tumors and the survival period of tumor bearing mice were observerd. Results Compared to spleen cells from mice immuniced with EL4 cells transfected with vector, spleen cells from mice immunized with HSA EL4 cells showed on enhanced proliferative response to the stimulation of HSA EL4 cells in a mixed lymphocyte tumor culture (MLTC) and also showed a significant anti tumor cytotoxicity to the parent tumor cell (EL4).HSA EL4 cells could be used as tumor vaccine to delay the growth of rumors and prolong the survival period of tumor bearing mice in the early stage,especially with low dose of IL2. Conclusions The expression of the co stimulatory molecule HSA on tumor cells can restore tumor cell immunogenicity.The tumor cells expressing HSA molecule can elicit an anti tumor immune respomse in vivo in a murine model.