CONTROLLED RELEASE POLYMERS FOR BRAIN TUMORS (U19 CA 528

由NCDDG成员发现和开发的可生物降解和生物相容性控释聚合物使我们能够绕过血脑的限制，使生长中的脑肿瘤长时间暴露在高浓度的药物中。这种方法可以有效地给药现有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、长期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，从而降低医疗保健费用。项目1 （Brem）将研究局部治疗脑肿瘤的最佳控释给药配方的有效性和安全性。项目2（兰格）将为选定的药剂提供聚合物配方。项目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）将开发适合结合到聚合物中用于局部治疗的化疗药物，并设计新的药物。项目5 （Pardoll）将聚合物传递细胞因子用于开发脑肿瘤疫苗。Core B （Vincek）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。国家发展与发展问题工作组的各方案一直作为一个有凝聚力的协作团体共同开展工作。我们的生产力反映在这个小组的许多新发现上，在过去的4年里，他们发表了236篇以上的论文，其中大部分涉及到项目之间的相互作用。这种合作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23年来FDA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，只有在额外的资金得到批准，以充分探索和发展这种治疗癌症的新方法的情况下，这种方法的真正前景才会实现。NCI正在为霍普金斯临床联盟资助一个单独的U01，以支持在NCDDG中开发的聚合物的I期测试。在NCI的持续支持和参与下，我们可以继续进行协同作用，并充分开发这种新方法的前景，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.