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ApoVax104-HPV as a Novel Vaccine for Cervical Cancer

ApoVax104-HPV 作为宫颈癌新型疫苗

基本信息

批准号：
7270778
负责人：
Kathryn J MacLeod
金额：
$ 30万
依托单位：
APOVAX, INC.
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-31 至 2008-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7270778
关键词：
ApoVax104 HPV Novel Vaccine Cervical

项目摘要

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.

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）的各种癌症疫苗已在临床前模型中显示出疗效。然而，它们的治疗功效在临床试验环境中相当有限。尽管这些疫苗临床无效的原因尚不清楚，但缺乏具有强效免疫刺激能力的佐剂、TAAs/TSA向专职抗原呈递细胞（APC）中的无效递送和/或存在显著的免疫逃避机制可能导致这种效应。这项建议的主要目的是开发一种新的宫颈癌癌症疫苗，克服这些问题。该疫苗命名为ApoVax 104-HPV，基于使用共刺激配体4-1BBL的专有制剂，旨在将TAAs/TSA特异性递送至APC。该疫苗制剂还激活APC以产生具有治疗功效的有效抗肿瘤免疫应答。这种新颖的专有分子由4-1BBL与核心链霉亲和素嵌合组成，并基于该公司的平台技术ProtEx（tm），由该应用的共同研究者Haval Shirwan博士发明。ApoVax 104技术在初步研究中已显示出对T效应细胞具有有效的免疫刺激活性，并对与肿瘤生长有关的T调节细胞具有抑制活性。将产生由与人乳头瘤病毒（HPV）-16病毒癌蛋白E7缀合的ApoVax 104组成的疫苗制剂，并测试其在C57 BL/6小鼠中诱导免疫应答的功效。成功完成拟议的实验将是ApoVax 104开发为ApoImmune第二代平台技术的关键路径的沿着第一步。如果ApoVax 104-HPV在这些初步的概念验证实验中证明有效，该公司将申请第二阶段SBIR授权，以进一步将ApoVax 104-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，ApoVax 104疫苗不仅可以预防癌症，还可以预防传染病，从而开发出一系列基于ApoVax 104的疫苗，这些疫苗具有数百万美元的巨大潜力。基于免疫系统的癌症治疗代表了经典化疗和放疗的替代治疗方法，并有望基于真正的癌症分子方法产生更明确的解决方案。ApoImmune的新型免疫系统疗法ApoVax 104疫苗是治疗癌症和恶性肿瘤疾病的一种新的创新方法。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A novel form of 4-1BBL has better immunomodulatory activity than an agonistic anti-4-1BB Ab without Ab-associated severe toxicity.

DOI：
10.1016/j.vaccine.2009.09.127
发表时间：
2009-12-11
期刊：
Vaccine
影响因子：
5.5
作者：
Schabowsky RH;Elpek KG;Madireddi S;Sharma RK;Yolcu ES;Bandura-Morgan L;Miller R;MacLeod KJ;Mittler RS;Shirwan H
通讯作者：
Shirwan H

4-1BB ligand as an effective multifunctional immunomodulator and antigen delivery vehicle for the development of therapeutic cancer vaccines.

DOI：
10.1158/0008-5472.can-09-4480
发表时间：
2010-05-15
期刊：
Cancer research
影响因子：
11.2
作者：
Sharma RK;Schabowsky RH;Srivastava AK;Elpek KG;Madireddi S;Zhao H;Zhong Z;Miller RW;Macleod KJ;Yolcu ES;Shirwan H
通讯作者：
Shirwan H

Costimulation as a platform for the development of vaccines: a peptide-based vaccine containing a novel form of 4-1BB ligand eradicates established tumors.