Goldman J M, Hibbin J, Kearney L, Orchard K, Th'ng K H
Br J Haematol. 1982 Nov;52(3):411-20. doi: 10.1111/j.1365-2141.1982.tb03910.x.
We studied the capacity of murine monoclonal antibodies with HLA-DR specificity to inhibit the proliferation in vitro of erythroid (BFU-E and CFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells in normal bone marrow and the blood of patients with chronic granulocytic leukaemia (CGL). Two IgG2 antibodies (CA 2.06 and L243) inhibited the proliferation of normal BFU-E and CFU-GM at relatively high dilution; a third antibody, DA2, had no effect on either progenitor cell. A complement-fixing monoclonal antibody with T-cell activity (OKT3) produced only minor reduction in progenitor cel proliferation. Further studies with L243 showed that BFU-E and CFU-GM from the blood of patients with CGL were inhibited to the same degree as normal marrow progenitor cells. The inhibition of progenitor cell proliferation by a given antibody was always complement dependent and was therefore presumed to be due to a direct cytotoxic effect. The inhibitory effect of monoclonal antibodies is a valuable approach to the characterization of antigenic determinants on myeloid progenitor cells and the differential cytotoxicity of selected monoclonal antibodies might be exploitable for therapy.
我们研究了具有HLA - DR特异性的鼠单克隆抗体抑制正常骨髓以及慢性粒细胞白血病(CGL)患者血液中红系祖细胞(BFU - E和CFU - E)和粒巨噬系祖细胞(CFU - GM)体外增殖的能力。两种IgG2抗体(CA 2.06和L243)在相对高的稀释度下可抑制正常BFU - E和CFU - GM的增殖;第三种抗体DA2对这两种祖细胞均无作用。一种具有T细胞活性的补体结合单克隆抗体(OKT3)仅使祖细胞增殖略有减少。对L243的进一步研究表明,CGL患者血液中的BFU - E和CFU - GM与正常骨髓祖细胞受到的抑制程度相同。特定抗体对祖细胞增殖的抑制始终依赖补体,因此推测是由于直接的细胞毒性作用。单克隆抗体的抑制作用是表征髓系祖细胞上抗原决定簇的一种有价值的方法,所选单克隆抗体的差异细胞毒性可能可用于治疗。