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Aluminum Oxide Nanoparticles Conjugated to Antigens Potently Induce Tumor Specifi

与抗原结合的氧化铝纳米颗粒可有效诱导肿瘤特异性

基本信息

批准号：
8688173
负责人：
Traci Leigh Hilton
金额：
$ 1.7万
依托单位：
UBIVAC, LLC
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8688173
关键词：
Acute Adjuvant Aluminum Hydroxide Aluminum Oxide Animals Antigens Autophagocytosis CD8B1 gene Cancer Etiology Cancer Vaccines Carcinoma Cessation of life Clinical Research Complex Coupled Cross Presentation Cross-Priming Cytotoxic T-Lymphocytes Data Dendritic Cells Developing Countries Development Disease Effectiveness FDA approved Future Goals HPV-High Risk Head Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Human Papilloma Virus Vaccine Human Papillomavirus Human papilloma virus infection Immune response Immunotherapy In Vitro Intellectual Property Journals Laboratories Legal patent Letters Licensing Malignant Neoplasms Malignant neoplasm of cervix uteri Measurable Measures Mediating Morbidity - disease rate Mus Nanotechnology Nature PGLA Phase I Clinical Trials Play Positioning Attribute Prevention Property Proteins Publications Publishing Research Role Small Business Innovation Research Grant T cell response T-Lymphocyte Technology Testing Time Toxic effect Translations Treatment Efficacy Tumor Antigens Tumor Burden Vaccination Vaccine Adjuvant Vaccines Viral Proteins Woman Work aluminum sulfate base biodegradable polymer cancer immunotherapy cancer type combat commercialization cytokine efficacy testing head-to-head comparison human UBE3A protein improved in vivo innovation meetings men metal oxide nanoparticle novel pre-clinical prophylactic public health relevance response therapeutic vaccine tumor vaccine delivery

项目摘要

DESCRIPTION (provided by applicant): PROJECT SUMMARY Although prophylactic vaccines have potential for prevention of high risk human papilloma virus (HPV) infection they have no therapeutic efficacy. It has been estimated that there will be no measurable decline of HPV- associated tumors before 2040 (Hellner et al., 2011). Likewise, other HPV-associated angogenital and head and neck cancers are predicted to afflict another 700,000 men and women over this period of time (Hellner et al., 2011). Therefore, research attempts to develop therapeutic vaccines to combat HPV-associated disease remains a high priority. In an on-going effort to improve tumor vaccine delivery and potency, our collaborator and co-founder, Dr. Hu, has discovered that nanoparticles coupled to antigens have significantly improved properties as vaccine carriers. When aluminum oxide (Al2O3) nanoparticles were compared head to head to alum (Rehydragel(R)), an FDA-approved vaccine adjuvant, Al2O3 nanoparticles were superior to alum at eliciting an antigen-specific T cell response and eradicating 7 day established tumors. The data presented here show a novel antigen carrier with adjuvant properties that activate dendritic cells to efficiently enhance cross-priming of T cells and improve the antitumor efficacy. UbiVac proposes to use aluminum oxide (Al2O3) nanoparticles conjugated to two known HPV tumor associated proteins E6 and E7 (NP-HPV vaccine) to elicit a strong CD8+ T cell immune response against HPV+ tumors. Successful completion of this project will provide proof-of-concept for treatment of HPV-associated carcinomas and a nanoparticle vaccine platform that can be utilized for other cancer types.

描述（由申请人提供）：项目总结尽管预防性疫苗具有预防高危人乳头瘤病毒（HPV）感染的潜力，但它们没有治疗效果。据估计，在2040年之前，HPV相关肿瘤将不会有可测量的下降（Hellner等人，2011年）。同样，预测其他HPV相关的血管生殖器癌和头颈癌在这段时间内将折磨另外700，000名男性和女性（Hellner et al.，2011年）。因此，开发治疗性疫苗以对抗HPV相关疾病的研究尝试仍然是高度优先事项。在持续努力改善肿瘤疫苗的递送和效力的过程中，我们的合作者和联合创始人胡博士发现，与抗原偶联的纳米颗粒作为疫苗载体具有显着改善的特性。当将氧化铝（Al 2 O3）纳米颗粒与明矾（FDA批准的疫苗佐剂）头对头比较时，Al 2 O3纳米颗粒在引发抗原特异性T细胞应答和根除7天建立的肿瘤方面上级明矾。本文提供的数据显示了一种具有佐剂性质的新型抗原载体，其活化树突状细胞以有效增强T细胞的交叉致敏并提高抗肿瘤功效。 UbiVac建议使用与两种已知的HPV肿瘤相关蛋白E6和E7（NP-HPV疫苗）结合的氧化铝（Al 2 O3）纳米颗粒，以引发针对HPV+肿瘤的强烈CD 8 + T细胞免疫应答。该项目的成功完成将为HPV相关癌症的治疗提供概念验证，并提供可用于其他癌症类型的纳米颗粒疫苗平台。