Electroporation-based delivery of a cancer DNA vaccine

描述(申请人提供)：宫颈癌是全球第二常见的女性癌症，由慢性人类乳头状瘤病毒(HPV)感染引起。由于癌前鳞状上皮内病变和宫颈癌持续表达HPV抗原，因此理论上可以通过治疗性疫苗接种治愈这种癌症。临床前研究和初步临床研究表明，为妇女接种治疗性疫苗是可行的。病变的根除是基于细胞介导的免疫反应。 人们积极寻求能够诱导针对广泛的HPV表位的细胞免疫的免疫策略。质粒DNA(PDNA)疫苗是一种很有吸引力的策略，因为它能够激发T细胞反应，而且一种疫苗中可以包括几种抗原。此外，质粒DNA经济、易于生产、存储和标准化，而且应该几乎不会产生副作用。 对于PDNA疫苗，给药方法对疗效至关重要。疫苗将通过电穿孔传递，因为这种方法提供了一致的、高水平的、可扩展的免疫原表达，这与强有力的、高幅度的免疫反应相关。 小鼠将用先前确定的针对HPV的多表位DNA疫苗进行免疫。终点将包括诱导T细胞反应，保护免受HPV诱导的肿瘤细胞的致命攻击，以及根除已建立的HPV诱导的肿瘤。

DESCRIPTION (provided by applicant): Cervical cancer, the second most common cancer in women worldwide, is caused by chronic human papilloma virus (HPV) infection. Since precancerous squamous intraepithelial lesions (SIL) and cervical cancer continuously express HPV antigens, this cancer is theoretically curable by therapeutic vaccination. Preclinical studies and preliminary clinical studies have indicated feasibility of therapeutic vaccination of women with SIL. Eradication of the lesions is based on cell-mediated immune response. Immunization strategies capable of inducing cellular immunity against a broad array of HPV epitopes are actively sought. Plasmid DNA (pDNA) vaccination represents an appealing strategy because of its ability to elicit T cell responses, and because several antigens can be included in a single vaccine. Also, plasmid DNA is economical, easy to produce, store and standardize, and should induce few, if any, side effects. For pDNA vaccines, the method of administration is critical for efficacy. Vaccine will be delivered by electroporation because this method provides consistent, high-level, scalable immunogen expression, which correlates with vigorous, high-magnitude immune responses. Mice will be immunized with a previously characterized polyepitope DNA vaccine against HPV. End points will include induction of T cell responses, protection against lethal challenge by HPV-induced tumor cells, and eradication of established HPV-induced tumors.