CONTROLLED RELEASE POLYMERS FOR BRAIN TUMORS (U19 CA 528

这个NCDDG的成员发现和开发了可生物降解和生物相容的控释聚合物，使我们能够绕过血脑的限制，并将生长中的脑肿瘤长时间暴露于高药物浓度。这种方法可以有效地管理现有的和合理设计的新药和生物制剂。药物在肿瘤生长部位的局部延长释放使肿瘤暴露于高水平的药物，最大限度地减少全身暴露和毒性，从而降低医疗保健成本。计划1（Brem）将研究用于脑肿瘤局部治疗的控释药物递送的最佳制剂的有效性和安全性。程序2（Langer）将提供选定药剂的聚合物配方。程序3（Saltzman）将构建用于预测药物在大脑中分布和清除的数学模型。项目4（Colvin）将开发适合掺入聚合物用于局部治疗的化疗药物，并设计新的药物。项目5（Pardoll）将聚合物递送细胞因子以开发脑肿瘤疫苗。核心B（Zurek）将提供用新方法制备的聚合物，并开发聚合物的放大和纯化。这个NCDDG的方案一直作为一个有凝聚力的合作小组共同努力。我们的生产力反映在这个小组的一些新发现中，在过去的4年里，他们已经发表了236篇论文，其中大部分涉及程序之间的相互作用。这种合作努力使我们能够设计和开展一系列临床前研究，以评估这种新的，潜在的，治愈性的癌症治疗方法，并导致FDA 23年来首次批准一种新的脑肿瘤治疗方法。根据我们的研究结果，目前正在进行另外28项临床试验。然而，只有批准额外的资金来充分探索和开发这种治疗癌症的新方法，才能实现这种方法的真正承诺。NCI正在为霍普金斯临床联盟资助一个单独的U01项目，以支持本NCDDG中开发的聚合物的I期试验。在NCI的持续支持和参与下，我们可以继续协同互动，充分发挥这种新方法的潜力，这将显著改变恶性胶质瘤患者的预后。

The discovery and development, by members of this NCDDG, of biodegradable and biocompatible controlled release polymers has enabled us to bypass the limitations of the blood-brain and expose the growing brain tumor to high drug concentrations for extended intervals. This approach can effectively administered current and rationally designed new drugs and biological agents. The local, prolonged release of drugs at the site of tumor growth exposes the tumor to high levels of the drug, minimizes systemic exposure and toxicity, and thus reduces health care costs. Program 1 (Brem) will investigate the effectiveness and safety of the best formulations of controlled-release drug delivery for local treatment of brain tumors. Program 2 (Langer) will provide polymer formulations for the selected agents. Program 3 (Saltzman) will construct mathematical models for predicting drug distribution and clearance in the brain. Program 4 (Colvin) will develop chemotherapy agents appropriate for incorporation into polymers for local therapy and design new agents. Program 5 (Pardoll) will polymer delivery of cytokines to develop brain tumor vaccines. Core B (Vincek) will provide polymers prepared with new methods and develop the scale-up and purification of the polymers. The programs of this NCDDG have been working together as a cohesive, collaborative group. Our productivity is reflected in a number of new discoveries by this group which has led to over 236 publications during the past 4 years, most of which involve interactions among the programs. This cooperative effort has allowed us to design and carry out a series of pre-clinical studies to evaluate this new, potentially, curative, cancer treatment, and resulted in the first approval in 23 years by the FDA of a new treatment for brain tumors. 28 additional clinical trials are currently underway based on our research findings. The true promise of this approach, however, will only be fulfilled if additional funding is approved to fully explore and develop this new approach to the treatment of cancer. The NCI is funding a separate U01 for a Hopkins Clinical Consortium to support Phase I testing of the polymers developed in this NCDDG. With ongoing support and participation of the NCI we can continue to interact synergistically and develop fully the promise of this new approach, which will significantly change the outcome for patients with malignant gliomas.