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.
Public Health Relevance Statement: Public Health Relevance: PROJECT NARRATIVE Human papilloma virus (HPV)-associated cervical cancer is the second largest cause of cancer death in women worldwide, and in developing countries, it is the number 1 cause of cancer deaths in women. Squamous Cell Carcinoma of the Head and Neck (SCCHN) is a devastating illness, the treatment of which is associated with significant morbidity. The goal of this proposal, "Aluminum Oxide Nanoparticles Conjugated to Antigens Potently Induce Tumor Specific T-Cells: An Innovative Approach to Cancer Immunotherapy", is to accelerate the translation and commercialization of a promising nanotechnology-derived cancer therapeutic vaccine for HPV-associated cancers.
NIH Spending Category: Bioengineering; Biotechnology; Cancer; Cervical Cancer; HIV/AIDS; HPV and/or Cervical Cancer Vaccines; Immunization; Infectious Diseases; Nanotechnology; Prevention; Sexually Transmitted Diseases/Herpes; Vaccine Related; Vaccine Related (AIDS)
Project Terms: Acute; Adjuvant; Aluminum Hydroxide; Aluminum Oxide; aluminum sulfate; Animals; Antigens; Autophagocytosis; base; biodegradable polymer; Cancer Etiology; cancer immunotherapy; cancer type; Cancer Vaccines; Carcinoma; CD8B1 gene; Cessation of life; Clinical Research; combat; commercialization; Complex; Coupled; Cross Presentation; Cross-Priming; cytokine; Cytotoxic T-Lymphocytes; Data; Dendritic Cells; Developing Countries; Development; Disease; Effectiveness; efficacy testing; FDA approved; Future; Goals; Head; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; head-to-head comparison; HPV-High Risk; Human papilloma virus infection; Human Papilloma Virus Vaccine; Human Papillomavirus; human UBE3A protein; Immune response; Immunotherapy; improved; In Vitro; in vivo; innovation; Intellectual Property; Journals; Laboratories; Legal patent; Letters; Licensing; Malignant neoplasm of cervix uteri; Malignant Neoplasms; Measurable; Measures; Mediating; meetings; men; metal oxide; Morbidity - disease rate; Mus; nanoparticle; Nanotechnology; Nature; novel; PGLA; Phase I Clinical Trials; Play; Positioning Attribute; pre-clinical; Prevention; Property; prophylactic; Proteins; public health relevance; Publications; Publishing; Research; response; Role; Small Business Innovation Research Grant; T cell response; T-Lymphocyte; Technology; Testing; therapeutic vaccine; Time; Toxic effect; Translations; Treatment Efficacy; tumor; Tumor Antigens; Tumor Burden; Vaccination; Vaccine Adjuvant; vaccine delivery; Vaccines; Viral Proteins; Woman; Work
