Application protocols for a cancer DNA vaccine

描述（申请人提供）：迫切需要能够诱导保护性抗肿瘤免疫的疫苗。质粒DNA（pDNA）疫苗接种代表了一种有吸引力的策略，因为它可以引发T细胞应答，这是抗肿瘤免疫的重要组成部分，并且因为几种抗原可以包含在单一疫苗中，从而最小化肿瘤逃逸的风险。而且，pDNA是经济的，易于生产和标准化，并且应该引起很少的副作用（如果有的话）。 在SBIR第一阶段，将探索一种新的pDNA癌症疫苗程序的可行性。将在使用含有鼠黑素瘤CTL表位的质粒免疫的小鼠中评估T细胞应答和针对肿瘤攻击的保护。疫苗接种将使用淋巴结内途径，这是众所周知的非常有效。疫苗将通过电穿孔递送，电穿孔是一种增加基因表达的幅度、持续时间和分布的递送方法。次级淋巴器官中抗原刺激的强度和持续时间是T细胞应答引发功效的主要决定因素。为了使反应最大化，将测试加强方案和遗传佐剂。 根据SBIR第二阶段，研究将包括在人类肿瘤抗原转基因小鼠中进行程序评估，开发适用于临床使用的输送装置，以及启动第一阶段临床试验

DESCRIPTION (provided by applicant): Vaccines capable of inducing protective antitumor immunity are urgently needed. Plasmid DNA (pDNA) vaccination represents an appealing strategy because it can elicit T cell responses, an essential component of antitumor immunity, and because several antigens can be included in a single vaccine, thus minimizing the risk of tumor escape. Also, pDNA is economical, easy to produce and standardize, and should induce few, if any, side effects. Under SBIR Phase I, a new pDNA cancer vaccine procedure will be explored for feasibility. T cell responses and protection against tumor challenge will be assessed in mice immunized using plasmids containing murine melanoma CTL epitopes. Vaccination will use the intra lymph node route, which is known as very efficient. Vaccine will be delivered by electroporation, a delivery method that increases magnitude, duration and distribution of gene expression. Strength and duration of antigenic stimulus in secondary lymphoid organs is a main determinant of priming efficacy of T cell responses. To maximize response, boosting regimes and genetic adjuvants will be tested. Under SBIR Phase II, studies will include procedure assessment in mice transgenic for human tumor antigens, development of a delivery device suitable for clinical use and initiation of a Phase I clinical trial