New Cancer Vaccine Technology Based on DRibbles Produced by Tumor Cells

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处理和呈递的理解。UBIVAC，LLC拥有技术(正在申请专利)的独家选择权，该技术利用了胡宏明博士开发的这些开发。此外，UBIVAC的创始人(胡博士和福克斯博士)和他们的合作者已经研究了可以显著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(点滴)相结合，进一步增加了肿瘤特异性T细胞的启动/扩增，并为点滴疫苗策略提供了显着的生存优势。基于UBIVAC第一阶段SBIR中产生的数据，启动了一项自体NSCLC点滴的试点临床试验(R21-CA123864)。这项由Investigator发起的试验刚刚开始，并已成功地为第一个符合条件的患者制造了自体点滴疫苗。UBIVAC，LLC有一个候选的非小细胞肺癌细胞系(腺癌)，它与其他七个筛选的非小细胞肺癌细胞系过度表达大量共同的基因，生长良好，并能很好地产生培养上清液。在SBIR第二阶段奖励开始之前，UBIVAC将使用上面列出的相同标准来鉴定第二个细胞系(鳞状细胞起源)，用于生产运球。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的无菌性能，生成WCBS并使用FDA批准的自体NSCLC Drobble Ind的CMC规格优化点滴生产，并生产足够的疫苗来完成48名患者的试验。目的2将进行多西他赛和异体非小细胞肺癌滴注疫苗联合GM-CSF或咪喹莫特(Dribble Plus)的随机II期试验。目的3将评估通用非小细胞肺癌滴注加疫苗诱导的体液免疫应答。它还将调查接种疫苗是否会减少循环肿瘤细胞(CTC)的数量，CTC是一种有可能替代临床反应的生物标志物。UBIVAC，LLC有一份意向书，如果拟议的第二阶段SBIR研究成功，可以提供200万至5000万美元支持运球技术的商业开发。为了帮助指导这一转变，UBIVAC组建了一个顾问委员会，成员包括一位拥有40多年医药经验的成功总裁/首席执行官；一位具有丰富医药肿瘤学经验的内科科学家，他曾担任全球疫苗和免疫调节剂主管；以及西北科技风险投资公司的董事总经理。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、转化性研究、商业和风险经验的个人、精心设计的随机第二阶段研究和尖端监测策略，这些策略极有希望改变非小细胞肺癌患者的生活，以及将该药物推向市场的经验。与公共卫生相关：UBIVAC的两种有前景的非小细胞肺癌滴注加疫苗(DPV-1+GM-CSF或咪喹莫特)的随机第二阶段临床试验的成功完成，将使UBIVAC能够“挑选赢家”，安排资金和/或战略合作伙伴，并提供令人信服的论据，将主导产品推进到晚期非小细胞肺癌的随机第三阶段临床试验。

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.