The Use of Novel Implantable Cancer Vaccines for the Treatment of Oral Cancer

描述(申请人提供)：口腔鳞状细胞癌(OSCC)是全球第六大常见癌症，占美国所有恶性肿瘤的2%。仅在今年，就有40,000名男性和女性患上口腔鳞状细胞癌，不幸的是，这些口腔鳞癌患者中只有三分之二能存活五年以上。在过去的几十年里，虽然消融/重建手术、放射治疗和化疗取得了进展，但口腔鳞癌患者的总体存活率并没有显著提高，而且在治疗过程中出现了多种并存的疾病，这可能会对生活质量产生负面影响。因此，确实需要创新的新方法来治疗口腔鳞状细胞癌。癌症免疫治疗作为一种新的癌症治疗方式已经出现，Mooney实验室已经开发出一种可植入的聚合物癌症疫苗，该疫苗在黑色素瘤和胶质瘤临床前模型中都显示出令人印象深刻的肿瘤杀伤力。我们的目标是评估这项有希望的癌症疫苗技术在口腔鳞癌中的应用。我们的总体假设是，能够为宿主树突状细胞提供适当的生物活性因子时空递呈的原位肿瘤疫苗可以诱导抗肿瘤免疫。这项建议中概述的研究旨在确定用于治疗口腔鳞状细胞癌的植入型癌症疫苗的有效性，优化癌症疫苗的各种成分以实现最大效力，并探索该疫苗与其他免疫治疗工具(如肿瘤特异性单抗)结合所产生的任何协同效应。总体而言，这些研究有望增强我们对树突状细胞和肿瘤特异性细胞毒性T细胞在口腔鳞癌治疗中所起作用的理解，并可能有助于口腔鳞癌新免疫疗法的发展。

DESCRIPTION (provided by applicant): Oral squamous cell cancer (OSCC) is the sixth most common cancer worldwide and accounts for 2% of all malignancies in the USA. In this year alone, 40,000 men and women will develop OSCC, and unfortunately, only two-thirds of these OSCC patients will survive more than five years. While the past decades have seen advances in ablative/reconstructive surgery, radiation therapy, and chemotherapy, the overall survival rate of OSCC patients has not improved significantly, and there are multiple co-morbidities which arise from treatment which may negatively affect quality of life. Thus, there is a real need for innovative new approaches to treating oral squamous cell cancer. Cancer immunotherapy has arisen as a novel treatment modality for several cancers, and an implantable, polymeric cancer vaccine has been developed by the Mooney laboratory which shows impressive tumor killing in both melanoma and glioma preclinical models. Our goal is to evaluate this promising cancer vaccine technology for use in oral squamous cell carcinoma. Our overall hypothesis is that an in situ cancer vaccine construct able to provide appropriate spatiotemporal presentation of bioactive factors to host dendritic cells can induce anti-tumor immunity. The studies outlined in this proposal seek to determine the effectiveness of the implantable cancer vaccine for treating OSCC, to optimize the various components of the cancer vaccine for maximum potency, and to explore any synergistic effects which arise by combining this vaccine with other immunotherapeutic tools such as tumor-specific monoclonal antibodies. Overall, these studies are anticipated to enhance our understanding of the role dendritic cells and tumor-specific cytotoxic T cells play in the treatment of OSCC, and may also contribute to the development of novel immunotherapies for OSCC.