TUMOR IMMUNOTHERAPY WITH BIODEGRADABLE MICROSPHERES

利用可生物降解微球进行肿瘤免疫治疗

• 批准号: 6916299
• 负责人: Thomas F Conway
• 金额: $ 63.7万
• 依托单位: THERAPYX, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-11-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6916299
• 关键词: antineoplastics; biodegradable product; cytokine; drug delivery systems; drug design /synthesis /production; drug screening /evaluation; interleukin 12; laboratory mouse; metastasis; method development; microcapsule; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; vaccine development; vaccine evaluation

DESCRIPTION (provided by applicant): Proof of principle for the feasibility of our proprietary tumor vaccination strategy involving the use of Interleukin-12-encapsulated microspheres has been demonstrated in Phase I studies. A single intra-tumoral injection of Interleukin-12-encapsulated biodegradable microspheres induces the complete regression of small primary tumors, promotes the development of long-term systemic anti-tumor immunity and results in the eradication of established disseminated disease in murine tumor models. In this Phase II application, we propose to perform extensive product development work, complete the toxicology/pharmacology studies and develop a clinical treatment protocol in preparation for IND filing. To this end, in Aims 1, 2 and 3, we will focus on product development studies including analytical assay development (Aim 1), process development for scale-up and stability analysis (Aim 2) and formulation development work to improve product stability (Aim 3). Pharmacokinetic and toxicological characterization of the product will be performed in Aim 4. In Aim 5, the optimized formulation will be used to evaluate the effect of dose, treatment schedule and booster vaccinations on long-term cure of disseminated disease in a pre-clinical routine tumor model. The optimal treatment strategy identified in Aim 5 will provide the blueprint for a Phase I clinical trial protocol. These studies are expected to generate the data that is necessary for IND approval.

描述（由申请人提供）： 在I期研究中，已经证明了我们专有肿瘤疫苗接种策略的可行性证明我们的专有肿瘤疫苗接种策略。白介素12封闭的可生物降解微球的单一肿瘤内注射可诱导小原发性肿瘤的完全回归，促进长期全身性抗肿瘤免疫的发展，并导致消除鼠类肿瘤模型中已建立的传播性疾病的消除。在此II阶段的应用中，我们建议进行广泛的产品开发工作，完成毒理学/药理学研究，并制定临床治疗方案，以准备IND归档。为此，在目标1、2和3中，我们将重点关注产品开发研究，包括分析测定开发（AIM 1），用于扩展和稳定性分析的过程开发（AIM 2）和配方开发工作以提高产品稳定性（AIM 3）。产品的药代动力学和毒理学表征将在AIM 4中进行。在AIM 5中，将使用优化的配方来评估剂量，治疗时间表和增强疫苗接种对在临床前常规肿瘤模型中长期治愈的长期治愈的影响。 AIM 5中确定的最佳治疗策略将为I期临床试验方案提供蓝图。这些研究有望生成IND批准所需的数据。