Aluminum Oxide Nanoparticles Conjugated to Antigens Potently Induce Tumor Specifi

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。

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.