ApoVax104-HPV as a Novel Vaccine for Cervical Cancer

描述(由申请人提供)：基于肿瘤相关抗原(TAA)或肿瘤特异性抗原(TSA)的各种癌症疫苗在临床前模型中显示出有效性。然而，在临床试验环境中，它们的治疗效果相当有限。虽然这些疫苗临床无效的原因尚不清楚，但缺乏具有强大免疫刺激能力的佐剂、将TAAs/TSA有效地输送到专业抗原提呈细胞(APC)和/或存在显著的免疫逃避机制可能是导致这种效果的原因之一。这项建议的主要目标是开发一种新的宫颈癌癌症疫苗，以克服这些问题。这种名为ApoVax104-HPV的疫苗基于共刺激配体4-1BBL的专利配方，该配方旨在专门将TAA/TSA递送到APC。该疫苗配方还激活APC，以产生具有治疗效果的有效抗肿瘤免疫反应。这种新颖的专利分子由4-1BBL与核心链霉亲和素嵌合而成，基于该公司的平台技术Protex(Tm)，该技术是由这一应用的共同研究者Haval Shirwan博士发明的。初步研究表明，ApoVax104技术对与肿瘤生长有关的T效应细胞具有强大的免疫刺激活性，对T调节细胞具有抑制活性。将生产一种由ApoVax104与人乳头瘤病毒(HPV)-16病毒癌蛋白E7偶联的疫苗配方，并测试其在C57BL/6小鼠中诱导免疫反应的有效性。拟议实验的成功完成将是ApoVax104作为Apo免疫的第二代平台技术开发的关键道路上的第一步。如果ApoVax104-HPV在这些初步概念验证试验中被证明有效，该公司将申请第二阶段SBIR拨款，以进一步将ApoVax104-HPV开发成领先的商业产品，在第一阶段临床试验中进行测试。此外，ApoVax104疫苗不仅可以预防癌症，还可以预防传染病，这导致了一系列基于ApoVax104的疫苗的开发，这些疫苗具有巨大的潜力，价值数百万美元。基于免疫系统的癌症治疗代表了经典化疗和放射治疗的另一种治疗方法，并有望在真正的分子治疗癌症的基础上产生更明确的解决方案。ApoImmune基于免疫系统的新疗法ApoVax104疫苗是治疗癌症和恶性肿瘤的一种新的创新方法。

DESCRIPTION (provided by applicant): Various cancer vaccines based on tumor associated antigens (TAAs) or tumor specific antigens (TSAs) have shown efficacy in preclinical models. However, their therapeutic efficacies have been rather limited in clinical trial settings. Although the reason for clinical inefficacy for these vaccines is not known, the lack of an adjuvant with potent immunostimulatory capacity, ineffective delivery of TAAs/TSAs into professional antigen presenting cells (APCs), and/or the presence of significant immune evasion mechanisms may contribute to this effect. The main objective of this proposal is to develop a novel cancer vaccine for cervical cancer which overcomes these problems. The vaccine, designated ApoVax104-HPV, is based on the use of a proprietary formulation of the costimulatory ligand, 4-1BBL, designed to specifically deliver TAAs/TSAs to APCs. This vaccine formulation also activates APCs for the generation of an effective anti-tumor immune response with therapeutic efficacy. This novel, proprietary molecule consists of 4-1BBL chimeric with core streptavidin and is based on the company's platform technology ProtEx(tm), invented by the co-investigator of this application, Dr. Haval Shirwan. The ApoVax104 technology has been shown in preliminary studies to have potent immunostimulatory activity for T effector cells and inhibitory activity for T regulatory cells that are implicated in tumor growth. A vaccine formulation consisting of ApoVax104 conjugated with the human papillomavirus (HPV)-16 viral oncoprotein E7 will be generated and tested for its efficacy to induce an immune response in C57BL/6 mice. Successful completion of the proposed experiments will be the first step along the critical path for the development of ApoVax104 as the second-generation platform technology for ApoImmune. If ApoVax104-HPV proves effective in these initial proof-of-concept experiments, the Company will apply for a Phase II SBIR grant to further develop ApoVax104-HPV into a lead commercial product to test in a Phase I clinical trial. In addition, ApoVax104 vaccines may not only protect against cancer but also against infectious diseases, leading to the development of an entire line of ApoVax104-based vaccines with significant potential in the millions of dollars. Immune system-based treatment of cancer represents an alternative therapeutic approach to classic chemotherapy and radiation treatment, and promises to yield a more definitive solution based on a true molecular approach to cancer. ApoImmune's novel immune system-based therapy, ApoVax104 vaccine, is a new, innovative approach to treating cancer and malignant neoplastic diseases.