CANCER THERAPY WITH BIOTHERAPEUTICS CONTAINING GENISTEIN

描述：（申请人的描述）拟议的长期目标 研究是开发新的和高效的生物治疗药物 治疗白血病淋巴瘤和乳腺癌 染料木黄酮 从假单胞菌属（Pseudomonasspp.） 是天然存在的 大豆中存在的酪氨酸激酶抑制剂。 的靶向递送 通过区域特异性连接到载体分子的染料木黄酮已被证明是 在人类癌症中诱导使徒细胞死亡的非常有效的策略 细胞（Uckun等人，Science 267：886-891，1995; Proc.Natl. 美国科学院 USA 92：9575-9579，1995）。 CD 19受体在细胞表面高水平表达， 白血病/淋巴瘤细胞，它与Src原癌基因物理相关 家族酪氨酸激酶形成膜相关抗凋亡 配合物 表皮生长因子受体（EGF-R）在高水平表达， 乳腺癌和前列腺癌细胞的水平， 与Src家族酪氨酸激酶相关， 膜相关抗凋亡复合物。 我们的初步研究 这有力地支持了我们关于CD 19和EGF受体是合适的假设 靶点的表面膜定向凋亡诱导策略， 将染料木黄酮递送至CD 19或EGF-R相关的重要酪氨酸激酶。 我们的临床项目的目标是开发和实施 使用B43-染料木黄酮作为 抗白血病剂和EGF-染料木黄酮作为抗乳腺癌剂。 它 预计（a）几种新的染料木黄酮缀合物将成为 在预计的资助期内可用于临床研究，以及（B） 建议的研究如能顺利完成，将会是一个良好的开始 朝向染料木黄酮缀合物用于更有效治疗的应用 白血病/淋巴瘤和乳腺癌患者。

DESCRIPTION: (Applicant's Description) The long-term goal of the proposed research is the development of novel and highly effective biotherapeutics against leukemias, lymphomas, and breast cancer. Genistein, an isoflavone from fermentation broth of Pseudomonas spp. is a naturally occurring tyrosine kinase inhibitor present in soybeans. The targeted delivery of genistein by regiospecific linkage to carrier molecules has proven to be a very effective strategy for inducing apostolic cell death in human cancer cells (Uckun et al., Science 267: 886-891, 1995; Proc. Natl. Acad Sci. USA 92: 9575-9579, 1995). CD19 receptor is expressed at high levels on leukemia/lymphoma cells and it physically associates with Src protooncogene family tyrosine kinases to form membrane-associated anti-apoptotic complexes. Epidermal growth factor receptors (EGF-R) are expressed at high levels on breast cancer as well as prostate cancer cells and they are also associated with Src family tyrosine kinases to form vital membrane-associated anti-apoptotic complexes. Our preliminary studies strongly support our hypothesis that CD 19 and EGF receptors are suitable targets for a surface membrane directed apoptosis-induction strategy by delivering Genistein to CD19- or EGF-R-associated vital tyrosine kinases. The goal of our Clinical Program is to develop and implement pharmacologically guided clinical Phase IM protocols using B43-genistein as an anti-leukemia agent and EGF-genistein as an anti-breast cancer agent. It is anticipated that (a) several novel genistein conjugates will become available for clinical studies during the projected grant period and (b) successful completion of the proposed studies will constitute a good start towards the application of genistein conjugates for more effective treatment of leukemia/lymphoma and breast cancer patients.