Immunoprevention and immunosurveillance of human non-viral cancers

摘要 我过去25年的研究在提供数据和科学方面是独一无二的 在研制非病毒性癌症预防疫苗的道路上发挥领导作用。癌症免疫治疗 现在已经成为现实，学术界和制药公司都在关注下一个最好的 晚期癌症的治疗。这是不幸的，因为即使像一些人一样成功 癌症免疫疗法最近被证明是有效的，它只对一小部分患者有帮助，甚至可以治愈 其中的一个较小的子集。它也是最昂贵的癌症治疗方法，使其不太可能 广泛提供给世界各地需要它的所有人。需要什么才能集中现场的注意力 关于免疫预防，有几个临床成功和相关的基础科学数据来帮助解释 这些，并指明了前进的道路。我的研究一直在提供这样的数据。目前我是 在临床试验中提供了第一批预防性癌症疫苗的例子。带着我的临床 同事们，在FDA的批准和NCI的支持下，我完成了世界上第一个临床试验 基于人类肿瘤抗原MUC1的疫苗在结肠癌高危人群中的应用 可行性研究使目前正在进行的第二次多中心、双盲、随机、 安慰剂对照疗效试验将于2016年春季完成。在分析这些问题时 我们正在获得新的数据，其中一些非常意想不到，对下一组 我计划开发的预防性癌症疫苗，但也适用于其他疫苗 和癌症免疫疗法。在接下来的七年里，我的计划将专注于学习 尽可能多地从我的第一次预防性疫苗试验中获得；定义控制 MUC1疫苗通过广泛的分子、细胞和免疫应答和潜在效力 外周血单核细胞和组织样本的蛋白质组学分析；2)提供支持其他癌前病变的数据 将病变作为预防癌症疫苗的候选者并设计新的癌症预防试验； 3)研制预防和控制癌症及病原体的通用疫苗。我们的 这项工作有望鼓励其他癌症免疫学家和免疫治疗师考虑 免疫预防非病毒性癌症是减少癌症流行的重要途径。

Abstract My research over the last 25 years has been unique in providing data and scientific leadership on the path towards a prevention vaccine for non-viral cancers. Cancer immunotherapy is now a reality and both academia and pharmaceutical companies are focusing on the next best treatment for advanced cancer. This is unfortunate given the fact that even as successful as some cancer immunotherapy was recently shown to be, it helps only a fraction of patients and cures even a smaller subset of those. It is also the most expensive cancer treatment making it less likely to be broadly available to all who need it around the world. What is needed to focus attention of the field on immunoprevention are a few clinical successes and relevant basic science data to help interpret those and point a path forward. My research has been providing such data. Currently I am providing first examples of preventative cancer vaccines in clinical trials. With my clinical colleagues, FDA approval and NCI support, I completed the first in the world clinical trial testing a vaccine based on a human tumor antigen MUC1 in people at high risk for colon cancer This feasibility study enabled the second, currently ongoing, multi-center, double-blind, randomized, placebo controlled efficacy trial that will complete accrual in the Spring of 2016. In analyzing these trials we are obtaining new data, some of it very unexpected, important for the next set of preventative cancer vaccines that I am planning to develop, but also applicable to other vaccines and cancer immunotherapies. In the next seven years, my program will be focused on 1) Learning as much as possible from my first preventative vaccine trials; defining parameters controlling the response to and potential efficacy of the MUC1 vaccine through extensive molecular, cellular and proteomic analysis of PBMC and tissue samples; 2) Providing data in support of other premalignant lesions as candidates for preventative cancer vaccines and designing new cancer prevention trials; 3) Developing a universal vaccine for prevention and control of cancer as well as pathogens. Our work will hopefully encourage other cancer immunologists and immunotherapists to consider immunoprevention of non-viral cancers as an important approach to reducing the cancer epidemic.