CONTROLLED RELEASE POLYMERS FOR BRAIN TUMORS (U19 CA 528

NCDDG成员发现和开发了可生物降解和生物兼容的控释聚合物，使我们能够绕过血液-大脑的限制，并将不断生长的脑瘤长期暴露在高浓度的药物下。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。在肿瘤生长部位局部长期释放药物使肿瘤暴露在高水平的药物下，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)将调查用于局部治疗脑肿瘤的最佳控释药物制剂的有效性和安全性。项目2(Langer)将为选定的试剂提供聚合物配方。程序3(Saltzman)将构建预测药物在大脑中的分布和清除的数学模型。项目4(Colvin)将开发适合于结合到聚合物中进行局部治疗的化疗药物，并设计新的药物。计划5(Pardoll)将聚合细胞因子的输送，以开发脑瘤疫苗。CORE B(Vincek)将提供用新方法制备的聚合物，并发展聚合物的放大和提纯。NCDDG的项目一直作为一个具有凝聚力和协作性的小组进行合作。我们的生产力反映在该团队的许多新发现中，这些发现导致在过去4年中发表了236多篇文章，其中大部分涉及项目之间的互动。这一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、可治愈的癌症治疗方法，并导致FDA 23年来首次批准一种治疗脑瘤的新方法。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，只有在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的情况下，这种方法的真正承诺才会实现。NCI正在为霍普金斯临床联盟资助一个单独的U01，以支持在这个NCDDG中开发的聚合物的第一阶段测试。在NCI的持续支持和参与下，我们可以继续协同互动，充分发展这一新方法的前景，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.