New Cancer Vaccine Technology Based on DRibbles Produced by Tumor Cells

基于肿瘤细胞产生的滴落物的新型癌症疫苗技术

基本信息

批准号：
8120195
负责人：
Sandra Aung
金额：
$ 67.23万
依托单位：
UBIVAC, LLC
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-06-01 至 2014-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8120195
关键词：
Accounting Adenocarcinoma Agonist Allogenic Animal Model Animals Antibody Formation Antigen Presentation Pathway Antigen-Presenting Cells Antigens Antitumor Response Autologous Award Binding Biological Assay Biological Markers Bulla Businesses CD8B1 gene Cancer Vaccines Cell Count Cell Line Cells Cellular Immunology Clinical Clinical Treatment Clinical Trials Clinical Trials Design Combined Vaccines Cross-Priming Data Dendritic Cells Detection Development Elements Evaluation FDA approved Foxes Funding Generations Genes Genetic Transcription Granulocyte-Macrophage Colony-Stimulating Factor Head Health Human Imiquimod Immune response Immunologics Immunotherapy In Vitro Incubated Individual Infectious Agent Lead Legal patent Letters Licensing Life Malignant Neoplasms Marketing Mediating Modeling Monitor Mus Non-Small-Cell Lung Carcinoma Patients Peptides Phase Phase II Clinical Trials Phase III Clinical Trials Physicians Procedures Process Production Proteasome Inhibitor Protein Biosynthesis Proteins Quality Control Randomized Regulatory T-Lymphocyte Research Personnel Scientist Small Business Innovation Research Grant Source Staging Sterility T-Lymphocyte Technology Testing Therapeutic Translating Translational Research Translations Treatment Efficacy Tumor Antigens Tumor Expansion Tumor-Derived Vaccination Vaccine Production Vaccines Waste Products base cell bank design docetaxel experience in vivo killings multicatalytic endopeptidase complex neoplastic cell novel oncology phase 2 study polypeptide pre-clinical protein degradation protein misfolding research study response scale up tumor vaccine safety

项目摘要

DESCRIPTION (provided by applicant): Recent advances in cellular immunology have revolutionized our understanding of antigen processing and presentation. UBIVAC, LLC, has an exclusive option on technology (patent pending) that exploits these developments that was developed by Dr. Hong-Ming Hu. Further, the founders of UBIVAC (Drs. Hu and Fox) and their collaborators have investigated additional treatment combinations that can significantly augment the therapeutic efficacy of vaccines. The combination of these strategies with this vaccine technology (DRibbles) in preclinical animal models further increased priming/expansion of tumor-specific T cells and provided a significant survival advantage for the DRibble vaccine strategy. Based on the data generated in UBIVAC's Phase I SBIR, a pilot Clinical Trial of Autologous NSCLC DRibbles was initiated (R21-CA123864). This Investigator-initiated trial just opened and autologous DRibble vaccine has been successfully made for the first eligible patient. UBIVAC, LLC, has one candidate NSCLC cell line (adenocarcinoma) that over expresses a large number of genes in common with seven other NSCLC cell lines screened, grows well and is a good producer of supernatant DRibbles. Before this SBIR Phase II award is initiated, UBIVAC will use the same criteria listed above to identify a second cell line (of squamous origin) for production of DRibbles. In Aim 1 UBIVAC will generate a master cell bank (MCB) for each cell line, test the MCBs for sterility, generate WCBs and optimize DRibble production using CMC specifications from the FDA-approved autologous NSCLC DRibble IND and produce sufficient vaccine to complete the 48 patient trial. Aim 2 will conduct a randomized phase II trial of docetaxel and allogeneic NSCLC DRibble vaccine combined with either GM-CSF or imiquimod (DRibble Plus) Aim 3 will evaluate the humoral immune response induced by Universal NSCLC DRibble Plus vaccine. It will also investigate whether vaccination reduces the number of circulating tumor cells (CTC), a biomarker that has the potential to be a surrogate for clinical response. UBIVAC, LLC has a letter of intent that could provide 2 to 50 million dollars to support the commercial development of DRibble technology if the proposed phase II SBIR study is successful. To help guide this transition UBIVAC has assembled an advisory board that includes a successful president/CEO with more than 40 years Pharma experience; a physician- scientist with large Pharma oncology experience who served as Global Head Vaccines & Immunomodulatory Agents; and the managing Director of Northwest Technology Ventures. Taken together, UBIVAC has the critical elements, compelling preclinical data, Individuals with substantial clinical, translational research, business and venture experience, a well designed randomized phase II study and cutting edge monitoring strategies that hold great promise to make a difference in the lives of patients with NSCLC, and the experience to get this agent to market. PUBLIC HEALTH RELEVANCE: Successful completion of the randomized Phase II clinical trial of UBIVAC's two promising NSCLC Dribble Plus vaccines (DPV-1 + GM-CSF or imiquimod) will allow UBIVAC to "pick-the-winner", arrange funding and/or a strategic partner and provide a compelling argument to move the lead product forward into a randomized Phase III clinical trial for advanced NSCLC.

描述（由申请人提供）：细胞免疫学的最新进展彻底改变了我们对抗原加工和呈递的理解。 UBIVAC, LLC 拥有独家技术选项（正在申请专利），该技术利用了由 Hong-Ming Hu 博士开发的这些成果。此外，UBIVAC 的创始人（胡博士和福克斯）及其合作者研究了可以显着增强疫苗治疗效果的其他治疗组合。这些策略与临床前动物模型中的疫苗技术 (DRibbles) 相结合，进一步增加了肿瘤特异性 T 细胞的引发/扩增，并为 DRibble 疫苗策略提供了显着的生存优势。根据 UBIVAC I 期 SBIR 中生成的数据，启动了自体 NSCLC DRibbles 的试点临床试验 (R21-CA123864)。这项由研究者发起的试验刚刚开始，自体 DRibble 疫苗已成功为第一位符合条件的患者制成。 UBIVAC, LLC 有一种候选 NSCLC 细胞系（腺癌），该细胞系过度表达大量与筛选的其他 7 种 NSCLC 细胞系相同的基因，生长良好，并且是上清液 DRibbles 的良好产生者。在启动 SBIR II 期授予之前，UBIVAC 将使用上面列出的相同标准来确定用于生产 DRibbles 的第二种细胞系（鳞状来源）。在目标 1 中，UBIVAC 将为每个细胞系生成一个主细胞库 (MCB)，测试 MCB 的无菌性，生成 WCB 并使用 FDA 批准的自体 NSCLC DRibble IND 中的 CMC 规格优化 DRibble 生产，并生产足够的疫苗来完成 48患者试验。目标 2 将进行多西他赛和同种异体 NSCLC DRibble 疫苗联合 GM-CSF 或咪喹莫特 (DRibble Plus) 的随机 II 期试验。目标 3 将评估通用 NSCLC DRibble Plus 疫苗诱导的体液免疫反应。它还将研究疫苗接种是否会减少循环肿瘤细胞（CTC）的数量，循环肿瘤细胞是一种有潜力替代临床反应的生物标志物。 UBIVAC, LLC 已签署意向书，如果拟议的 II 期 SBIR 研究取得成功，则可以提供 2 至 5000 万美元来支持 DRibble 技术的商业开发。为了帮助指导这一转变，UBIVAC 组建了一个顾问委员会，其中包括一位拥有 40 多年制药经验的成功总裁/首席执行官；一位拥有丰富肿瘤药学经验的医师科学家，曾担任疫苗和免疫调节剂全球负责人；兼西北科技风险投资公司董事总经理。总而言之，UBIVAC 拥有关键要素、令人信服的临床前数据、具有丰富临床、转化研究、商业和风险投资经验的个人、精心设计的随机 II 期研究和尖端监测策略，这些都有望改变人们的生活。 NSCLC 患者，以及将该药物推向市场的经验。公共健康相关性：成功完成 UBIVAC 两种有前景的 NSCLC Dribble Plus 疫苗（DPV-1 + GM-CSF 或咪喹莫特）的随机 II 期临床试验将使 UBIVAC 能够“挑选获胜者”、安排资金和/或战略合作伙伴，并提供令人信服的论据，推动主导产品进入晚期 NSCLC 的随机 III 期临床试验。