Aluminum Oxide Nanoparticles Conjugated to Antigens Potently Induce Tumor Specifi

项目概述：虽然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年前，与HPV相关的肿瘤不会显著下降(Hellner等人，2011年)。同样，其他与HPV相关的生殖器癌和头颈癌预计将在这段时间内折磨另外70万男性和女性(Hellner等人，2011年)。因此，试图开发治疗性疫苗来对抗HPV相关疾病的研究仍然是一个高度优先的问题。在改进肿瘤疫苗递送和效力的持续努力中，我们的合作者兼联合创始人胡博士发现，与抗原偶联的纳米颗粒显著改善了作为疫苗载体的性能。当将氧化铝纳米颗粒与美国食品和药物管理局批准的疫苗佐剂--氧化铝(Rehyglel(R))--进行头对头比较时，在激发抗原特异性T细胞反应和根除7天内已建立的肿瘤方面，氧化铝纳米颗粒优于明矾。本文提供的数据显示了一种具有佐剂特性的新型抗原载体，它可以激活树突状细胞，有效地增强T细胞的交叉激发，提高抗肿瘤效果。 UbiVac建议使用连接到两个已知的HPV肿瘤相关蛋白E6和E7(NP-HPV疫苗)的氧化铝纳米颗粒来诱导针对HPV+肿瘤的强大CD8+T细胞免疫反应。该项目的成功完成将为HPV相关癌症的治疗提供概念验证，并提供一个可用于其他癌症类型的纳米颗粒疫苗平台。

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.