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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。
Objective To investigate the effect of 4-1BB extracellular membrane protein on anti-tumor effect of anti-CD3 / anti-Pgp micro-bifunctional antibody. Purified human 4-1BBL fusion protein and anti-CD3 / anti-Pgp micro-bifunctional antibody were expressed in vitro. CytoTox96 was used to detect the extracellular fusion protein of human 4-1BBL, anti-CD3 / anti-Pgp micro-bifunctional antibody PBL on the target cells K562 / A02 cells in vivo, nude mouse xenograft models were established in vivo to detect the 4-1BBL extracellular domain protein as an immunomodulatory protein to enhance anti-tumor effect of anti-CD3 / anti-Pgp PBL. Results The extracellular fusion protein of 4-1BBL could enhance the killing effect of anti-CD3 / anti-Pgp and PBL on target cell K562 / A02 in vitro and enhance anti-tumor effect of anti-CD3 / anti-Pgp based on PBL in vivo. Conclusion Soluble 4-1BBL may be a promising biotherapeutic adjuvant that helps PBLs target tumor cells more efficiently.