ERADICATION OF RESIDUAL LEUKEMIA BY ANTIBODY THERAPY

抗体免疫治疗肿瘤的实验动物和动物实验研究 对人类患者的研究一直是人们强烈感兴趣的焦点 调查了几十年。我们的长期目标是 了解抗体依赖的细胞破坏的机制 靶细胞，并将这一知识应用于治疗 肿瘤疾病，特别是急性髓细胞白血病(AML)。 我们已经评估了抗体治疗的可行性。 根除白血病中残留的少量AML细胞 大鼠接受强化化疗后骨髓 模拟人类急性髓系白血病患者的移植。我们使用了一个 可与大鼠和人急性髓系白血病细胞反应的单抗 从而使抗体对急性髓系白血病细胞和造血功能的影响 可以在大鼠体内测试祖细胞，然后再用这种抗体或 其他交叉反应抗体也被考虑用于临床。 在这项提议中，我们计划产生多个交叉反应 免疫球蛋白M和免疫球蛋白G亚型的单抗及其鉴定 抑制大鼠急性髓系白血病而不影响骨髓的能力 造血祖细胞。它们所识别的抗原 抗体的特征是正常细胞表达 抗原将被识别出来。这些化合物的体外活性 在不影响人骨骼的情况下抑制人AML细胞的抗体 将对骨髓细胞进行评估。我们将尝试加强 抗体依赖性急性髓系白血病的替代或非特异性抑制 能够破坏抗体致敏的激活效应细胞 急性髓系白血病细胞。我们认为交叉反应的单抗 治疗将有助于根除微小残留白血病 细胞，并为急性髓细胞白血病的治疗增加了许多。

Immunotherapy of cancer with antibody in experimental animals and in human patients has been a focus of intense interest and investigation for many decades. Our long-term goal is to understand the mechanisms of antibody-dependent destruction of target cells and apply this knowledge in the treatment of neoplastic disorders, particularly acute myelocytic leukemia (AML). We have evaluated the feasibility of antibody therapy in the eradication of a small number of residual AML cells in leukemic rats receiving intensive chemotherapy followed by bone marrow transplantation simulating human AML patients. We used a monoclonal antibody that reacted with both rat and human AML cells so that the effects of the antibody on AML cells and hematopoietic progenitor cells could be tested in rats before this antibody or other cross-reactive antibodies are considered for clinical use. In this proposal, we plan to produce multiple cross-reactive monoclonal antibodies of IgM and IgG isotypes, and evaluate their ability to suppress AML in rats without affecting bone marrow hematopoietic progenitor cells. The antigens recognized by these antibodies will be characterized and normal cells expressing the antigens will be identified. The in vitro activity of these antibodies to suppress human AML cells without affecting human bone marrow cells will be assessed. We will attempt to potentiate the antibody-dependent AML suppression by replacing or non-specifically activating effector cells capable of destroying antibody-sensitized AML cells. We believe that cross-reactive monoclonal antibody therapy will be useful for eradicating minimal residual leukemia cells and add much to the treatment of AML.