Aluminum Oxide Nanoparticles Conjugated to Antigens Potently Induce Tumor Specifi

虽然预防性疫苗有预防高危人乳头瘤病毒（HPV）感染的潜力，但没有治疗效果。据估计，在2040年之前，HPV相关肿瘤的数量不会出现可测量的下降（Hellner et al., 2011）。同样，预计在此期间，其他与hpv相关的血管生殖系统和头颈部癌症将影响另外70万男性和女性（Hellner et al., 2011）。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一个高度优先事项。在持续的努力，以提高肿瘤疫苗的递送和效力，我们的合作者和联合创始人，胡博士，已经发现纳米颗粒偶联抗原有显著改善的性质作为疫苗载体。当氧化铝（Al2O3）纳米颗粒与明矾（Rehydragel(R)）（一种fda批准的疫苗佐剂）进行头部比较时，Al2O3纳米颗粒在引发抗原特异性T细胞反应和根除7天内建立的肿瘤方面优于明矾。这里的数据显示了一种具有佐剂特性的新型抗原载体，可以激活树突状细胞，有效地增强T细胞的交叉启动，提高抗肿瘤效果。

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.