Kvalheim G, Sørensen O, Fodstad O, Funderud S, Kiesel S, Dörken B, Nustad K, Jakobsen E, Ugelstad J, Pihl A
Department of Tumor Biology, Institute for Cancer Research, Oslo, Norway.
Bone Marrow Transplant. 1988 Jan;3(1):31-41.
B-lymphoma cells were purged from human bone marrow by incubating the cell suspension with a cocktail of three different pan-B cell mouse IgG1 monoclonal antibodies, and then with immunobeads charged with sheep anti-mouse antibody, followed by magnetic separation. The primary antibodies used, HD37 (CD19), HD6 (CD22), and HH1 (CD37), bind to a very high percentage of the cells in non-Hodgkin's lymphomas of poor prognosis. The secondary antibody is directed against the Fc portion of the IgG antibodies. In model experiments Burkitt's lymphoma cells (Rael) were admixed to mononuclear bone marrow cells in the ratio 1/9. With a ratio of immunobeads/total antibody-binding B cells of 50/1 in a first treatment cycle and repeating the procedure with the same number of beads in a second cycle, a tumor cell depletion of more than 5 logs was achieved, as judged by a clonogenic assay. The concomitant reduction of CFU-GM and CFU-GEMM was about 20%. The purging procedure has been scaled up to clinical use. Equipment suitable for purging patients' marrow specimens, employing standard transfusion facilities, is described. With this equipment the efficacy of tumor cell removal was the same as in the model experiments, and the whole magnetic separation could be completed in 2 hours.
通过将细胞悬液与三种不同的全B细胞小鼠IgG1单克隆抗体混合孵育,然后与负载羊抗小鼠抗体的免疫磁珠孵育,接着进行磁分离,从人骨髓中清除B淋巴细胞瘤细胞。所使用的一抗HD37(CD19)、HD6(CD22)和HH1(CD37)可与预后不良的非霍奇金淋巴瘤中很高比例的细胞结合。二抗针对IgG抗体的Fc部分。在模型实验中,将伯基特淋巴瘤细胞(Rael)与单核骨髓细胞按1/9的比例混合。在第一个治疗周期中,免疫磁珠与总抗体结合B细胞的比例为50/1,并在第二个周期中用相同数量的磁珠重复该过程,通过克隆形成试验判断,肿瘤细胞清除率超过5个对数。CFU-GM和CFU-GEMM的相应减少约为20%。该清除程序已扩大到临床应用。描述了使用标准输血设备来清除患者骨髓标本的设备。使用该设备,肿瘤细胞去除效果与模型实验相同,整个磁分离过程可在2小时内完成。