ERADICATION OF RESIDUAL LEUKEMIA BY ANTIBODY THERAPY

用抗体在实验动物中进行癌症的免疫治疗， 在人类患者中的应用一直是人们强烈关注的焦点， 调查了几十年。 我们的长期目标是 了解抗体依赖性破坏的机制， 靶细胞，并将这些知识应用于治疗 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 在白血病患者中根除少量残留的AML细胞 接受强化化疗的大鼠， 模拟人类AML患者的移植。 我们使用了 与大鼠和人AML细胞反应的单克隆抗体 因此抗体对AML细胞和造血细胞的作用 祖细胞可以在这种抗体之前在大鼠中进行测试， 其它交叉反应性抗体被考虑用于临床应用。 在这个建议中，我们计划生产多个交叉反应， IgM和IgG同种型的单克隆抗体，并评估其 抑制大鼠AML而不影响骨髓的能力 造血祖细胞 这些识别的抗原 抗体将被表征，表达抗体的正常细胞将被表征。 抗原将被识别。 这些的体外活性 抑制人类AML细胞而不影响人类骨骼的抗体 将评估骨髓细胞。 我们将努力加强 通过替代或非特异性地抑制抗体依赖性AML 激活能够破坏抗体致敏的 AML细胞。 我们认为交叉反应性单克隆抗体 治疗将有助于根除微小残留白血病 细胞，并大大增加了AML的治疗。

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.