Monoclonal antibodies to carbohydrate antigens in autologous bone marrow transplantation.
Monoclonal antibodies to carbohydrate antigens in autologous bone marrow transplantation.
复制标题
自体骨髓移植中针对碳水化合物抗原的单克隆抗体。
DOI：
10.1002/jcb.240360412
复制
发表时间：
1988
影响因子：
4
通讯作者：
Howell,AL
中科院分区：
文献类型：
--
作者：
Ball,ED;Howell,AL
正常和恶性骨髓细胞表达一种高度免疫原性的寡糖，乳糖-n-岩藻五糖-III（LNF-III），已被许多单克隆抗体（MoAb）鉴定。我们一直对LNF-III的一种特殊单克隆抗体PM-81在治疗急性髓细胞性白血病患者中的应用感兴趣，该抗体在体外治疗骨髓。在用PM-81和另一种单克隆抗体AML-2-23体外处理骨髓后，剩余的细胞被用作接受高剂量化疗和放疗的患者的自体移植物。为了提高单克隆抗体对缓解期骨髓白血病细胞的杀伤能力，我们探讨了神经氨酸酶对白血病细胞的作用。在本文中，我们描述了通过免疫荧光表达低水平LNF-III的髓性白血病细胞在神经氨酸酶处理后可以显示出高水平的LNF-III。此外，我们发现正常骨髓祖细胞不具有隐蔽的LNF-III抗原，从而允许将这一发现应用于临床环境。此外，我们已经表明，来自一名急性髓性白血病患者的白血病集落形成细胞表达隐藏的LNF-III，并且在暴露于神经氨酸酶后，在补体存在下PM-81消除这些集落形成细胞的能力增加。这些数据表明，LNF-III部分几乎普遍表达于髓性白血病细胞及其祖细胞上，但不表达于正常祖细胞上。因此，有可能通过骨髓神经氨酸酶处理来增强体外白血病细胞杀伤。
Normal and malignant myeloid cells express a highly immunogenic oligosaccharide, lacto‐n‐fucopentaose‐III (LNF‐III), that has been identified by numerous monoclonal antibodies (MoAb). We have been interested in the use of a particular monoclonal antibody to LNF‐III, PM‐81, in the treatment of patients with acute myelogenous leukemia using the antibody to treat bone marrow in vitro. Following in vitro treatment of bone marrow with PM‐81 and another MoAb, AML‐2–23, the remaining cells are used as an autograft in a patient treated with high‐dose chemotherapy and radiotherapy. In order to enhance the ability of the MoAb to lyse leukemic cells in the remission bone marrow, we have explored the effect of neuraminidase treatment on leukemia cells. In this paper we describe that myeloid leukemia cells expressing low levels of LNF‐III by immunofluorescence can be shown to have high levels of LNF‐III after neuraminidase treatment. In addition, we show that normal bone marrow progenitor cells do not have cryptic LNF‐III antigen, thus allowing the application of this finding to the clinical setting. Moreover, we have shown that leukemia colony‐forming cells from one patient with acute myelogenous leukemia express cryptic LNF‐III and that after exposure to neuraminidase there was an increased ability of PM‐81 in the presence of complement to eliminate these colony forming cells. These data indicate that the LNF‐III moiety is almost universally expressed on myeloid leukemia cells and their progenitors but not expressed on normal progenitors. Thus, it may be possible to enhance leukemia cell kill in vitro by neuraminidase treatment of bone marrow.