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加工和呈递的理解。UBIVAC， LLC拥有独家技术选择权（专利申请中），该技术利用了由胡洪明博士开发的这些发展。此外，UBIVAC的创始人(dr。Hu和Fox)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。在临床前动物模型中，这些策略与这种疫苗技术（DRibbles）的结合进一步增加了肿瘤特异性T细胞的启动/扩增，并为DRibble疫苗策略提供了显著的生存优势。基于UBIVAC I期SBIR产生的数据，启动了一项自体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疫苗已经成功地为第一个符合条件的患者生产出来。UBIVAC， LLC有一种候选的非小细胞肺癌细胞系（腺癌），与筛选的其他7种非小细胞肺癌细胞系一样，过度表达大量基因，生长良好，是上清滴的良好产生者。在SBIR II期合同启动之前，UBIVAC将使用上面列出的相同标准来确定第二个用于DRibbles生产的细胞系（鳞状起源）。在Aim 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的CMC规格优化DRibble生产，并生产足够的疫苗来完成48例患者试验。Aim 2将进行多西他赛和异基因NSCLC DRibble疫苗联合GM-CSF或咪喹莫特（DRibble Plus）的随机II期试验。Aim 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，这是一种有可能成为临床反应替代品的生物标志物。UBIVAC， LLC有意向书，如果拟议的II期SBIR研究成功，将提供200万至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；拥有丰富的制药肿瘤学经验，曾担任全球疫苗和免疫调节剂负责人；也是西北科技风险投资公司的总经理。综上所述，UBIVAC具有以下关键要素：引人注目的临床前数据、具有丰富临床、转化研究、商业和风险经验的个体、精心设计的随机II期研究和尖端的监测策略，这些都有望改变NSCLC患者的生活，以及将该药物推向市场的经验。公共卫生相关性：UBIVAC两种有前景的NSCLC Dribble Plus疫苗（DPV-1 + GM-CSF或imiquimod）的随机II期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NSCLC的随机III期临床试验。

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.