中文摘要：

目的研究4-1BBL胞膜外区蛋白对抗CD3/抗Pgp微型双功能抗体抗肿瘤作用的影响。方法表达纯化人4-1BBL胞膜外区融合蛋白及抗CD3/抗Pgp微型双功能抗体,体外CytoTox96检测联合应用人4-1BBL胞膜外区融合蛋白、抗CD3/抗Pgp微型双功能抗体及PBL对靶细胞K562/A02细胞的杀伤作用,体内建立裸鼠移植瘤模型检测4-1BBL胞膜外区蛋白作为一种免疫调节蛋白,增强抗CD3/抗Pgp基于PBL的抗肿瘤效果。结果4-1BBL胞膜外区融合蛋白在体外能够增强抗CD3/抗Pgp及PBL对靶细胞K562/A02的杀伤作用,在体内能够增强抗CD3/抗Pgp基于PBL的抗肿瘤作用。结论可溶型4-1BBL可能成为一种有前景的生物治疗佐剂,有助于PBL更高效地靶向杀伤肿瘤细胞。

英文摘要：

To study effects of the human extracellular domain of 4-1BBL（ex4-1BBL） on antitumor activity of anti-CD3/anti-Pgp diabody.Ex4-1BBL and anti-CD3/anti-Pgp diabody were expressed in E.coli strain,and then the expression products were purified with affinity chromatography.Nonradioactived Cytotox 96 assay kit was used to observe the cytotoxicity of PBL regulated by ex4-1BBL and anti-CD3/anti-Pgp diabody in vitro with the their target cells（K562/A02）at different E：T ratio.The results demonstrated that ex4-1BBL enhanced the antitumor immunity of PBL against multidrug resistant K562/A02 transplanted in nude mice.Tumor growth was dramatically inhibited by the combined therapy of ex4-1BBL and anti-CD3/anti-Pgp.Our results demonstrated that soluble ex4-1BBL,as a immunoadjuvant, can modulate the PBL activation and enhance the outcomes of PBL-based antitumor biotherapy.Thus,ex4-1BBL may become a new agent for bio-immunotherapy.