Engineered Nano-formulations for STING Activation

用于 STING 激活的工程纳米制剂

• 批准号: 10661091
• 负责人: Yu Leo Lei
• 金额: $ 57.53万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-06 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10661091
• 关键词: Address; Advanced Malignant Neoplasm; Agonist; Animal Model; Animals; Benchmarking; Biological Response Modifiers; Breeding; Cancer Patient; Canis familiaris; Cells; Clinical Trials; Crystal Formation; Data; Dental; Dinucleoside Phosphates; Disease; Disseminated Malignant Neoplasm; Dose; Engineering; Excision; Formulation; Gene Activation; Genes; Genetic Engineering; Goals; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Human; Immune; Immune response; Immune system; Immunologic Stimulation; Immunotherapy; In Vitro; Injections; Interferons; Knowledge; Libraries; Lymphoid Tissue; Malignant Neoplasms; Manganese; Mediating; Modeling; Mus; National Institute of Dental and Craniofacial Research; Nature; Neoplasm Metastasis; Oral; Pathway interactions; Patients; Periodicity; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Pharmacologic Substance; Property; Public Health; Race; Rattus; Research; Resistance; Role; Safety; Sampling; Serum; Spleen; System; Therapeutic; Toxic effect; Toxicology; Treatment Efficacy; Tumor Immunity; anti-PD-1; anti-PD1 therapy; antitumor effect; craniofacial; design; efficacy evaluation; immune activation; immune checkpoint blockade; immunomodulatory strategy; immunoregulation; intravenous administration; malignant mouth neoplasm; mouse model; nano; nanocrystal; nanoengineering; nanoformulation; nanomaterials; nanoparticle; new technology; next generation; novel; particle; particle therapy; response; success; tumor

Abstract Head and neck squamous cell carcinoma (HNSCC) is an extremely aggressive disease with poor overall survival. Despite the success of immune checkpoint blockade (ICB), the current forms of immunotherapy benefit only less than 15% of HNSCC patients. Therefore, there exists a critical need for new strategies for achieving powerful immune responses. STING (stimulator of IFN genes) is considered one of the key immune regulators that could convert non-responders to responders. Given the critical role of the STING pathway in cancer immunity, many pharmaceutical companies are racing to establish their discovery pipelines for STING agonists. However, conventional STING agonists have major limitations. Most STING agonists in clinical trials now are administrated via intratumoral injection due to their poor pharmaceutical properties. This precludes their applicability for the treatment of metastatic cancer. Therefore, there is an urgent need to identify and develop new STING agonists that can eliminate advanced cancer in an effective and safe manner. Here, we propose to develop the next- generation STING agonist nanoparticles with potent anti-tumor efficacy, favorable pharmaceutical properties, and acceptable safety profiles. We will develop novel STING agonist-based therapeutics and evaluate their efficacy in advanced animal models and perform large animal toxicity studies.

摘要