Gene and Immunotherapy of Neoplasms Affecting Human Communication

本项目的目的是阐明上呼吸消化道鳞状细胞肿瘤的分子和免疫发病机制，并使这些疾病的分子和免疫治疗方法的发展。 已经开发了人和鼠鳞状细胞癌细胞系模型，并使用分子和免疫测定来鉴定随着肿瘤进展而差异表达的基因。 促炎细胞因子、相关信号转导通路分子和即刻早期转录因子基因已被证明随着肿瘤进展而过表达或激活，并且与侵袭性生长和转移相关。 这些候选基因的功能后，过表达或抑制转染的肿瘤与显性负结构已成为最近的调查，以确定潜在的分子和免疫治疗的目标。基于由这些肿瘤产生的细胞因子破坏免疫应答的假设，用重组和病毒转导的免疫调节细胞因子治疗后的抗原识别和保护性免疫应答的激活的研究一直在进行中。 与路易斯维尔大学的研究人员合作开发了第一个用于免疫治疗研究的口腔癌同基因小鼠模型。 这些研究已经鉴定出三种具有抗肿瘤活性的细胞因子。 免疫的细胞机制和识别的抗原的分子结构将是未来研究的主题，以确定使用这些细胞因子的疗法或疫苗是否适用于人体临床试验。

The purpose of this project is to elucidate the molecular and immune pathogenesis of squamous cell neoplasms of the upper aerodigestive tract, and to enable the development of approaches for molecular and immune therapy for these disorders. Human and murine squamous cell carcinoma cell line models have been developed and used to identify genes that are differentially expressed with tumor progression using molecular and immune assays. Proinflammatory cytokines, related signal transduction pathway molecules, and immediate early transcription factor genes have been shown to be overexpressed or activated with tumor progression, and are associated with aggressive growth and metastasis. The function of these candidate genes following overexpression or inhibition by transfection of tumors with dominant negative constructs has been the subject of recent investigations to identify potential targets for molecular and immune therapy. Based upon the hypothesis that the cytokines produced by these neoplasms disrupt the immune response, studies of antigen recognition and activation of protective immune responses following treatment with recombinant and virally transduced immunoregulatory cytokines have been ongoing. The first syngeneic murine model of oral carcinoma for study of immune therapy was developed in collaboration with investigators from the University of Louisville. These studies have resulted in the identification of three cytokines with anti-tumor activity. The cellular mechanisms of immunity and molecular structure of the antigens recognized will be the subject of future investigations to determine whether therapies or vaccines using these cytokines may be suitable for human clinical trials.