激发型4-1BBL单抗在体内对人白血病系胞系SHI-1生物学行为的影响

Effects of the monoclonal antibody against the provocative type of human 4-1BB on the biological characteristics of the monocytic leukemia cell line SHI-1

通过激发型4-1BBL单抗作用于人M5型白血病-SCID小鼠模型,研究4-1BBL/4-1BB逆向信号在体内对M5型白血病细胞系SHI-1生物学行为的影响。将1×106SHI-1细胞移植至SCID小鼠腹腔,经1F1单抗作用,于移植30 d后小鼠尾静脉取血并采用流式细胞术(FCM)监测4-1BBL阳性细胞表达率。于移植42 d后处死小鼠,通过病理组织学检查和FCM,分析SCID小鼠的骨髓、外周血、肝脏和脾脏中白血病细胞的浸润及病理变化。结果:各组小鼠腹腔均可发现瘤块生长。单抗作用组小鼠肿块出现较早,生长速度较快,其主要组织器官更发现有肿瘤细胞的浸润。1F1单抗在体内可促进SHI-1细胞的增殖与迁移,这为研究M5型白血病的发生与发展提供了理论依据。

To investigate the effects and mechanism of the 4-1BB reverse signaling on the monocytic leukemia cell line SHI-1 of severe combined immunodeficiency（SCID） mice, the SHI-1/SCID mouse model was established by interperitoneal injection with 1 × 10^6 SHI-1 cells into SCID mice. Seven days after transplantation, the 1F1 monoclonal antibody prepared in our laboratory was injected into mice intra-peritoneally, and serial tail vein blood samples at regular intervals were taken to detect the expression of 4-IBB ligand（4-IBBL） on SWHI-1 cells by flow cytometry（FCM）. Forty two days after transplantation, all the experimental mice were killed and the infiltration with leukemia cells as well as the pathologic changes in bone marrow, peripheral blood, liver and spleen of SCID mice were analyzed by means of immunohistochemical examinations and FCM assay. It was found that growth of tumor masses in peritoneal cavity could be demonstrated in various groups of experiments in mice, in which the growth of tumor masses appeared early and fast in case of mice treated with monoclonal antibody than that of the contro.1 mice, and infiltration with tumor cells could be found on the chief organs. It is concluded that 4-IBBL reverse signaling can promote the proliferation and migration of SHI-1 cells in vivo. This result may be significant for the biological study and treatment of acute monocytic leukemia.