GENE AND IMMUNOTHERAPY OF NEOPLASMS AFFECTING HUMAN COMMUNICATION

本项目的目的是阐明上呼吸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成为可能。人和小鼠鳞状细胞癌细胞系模型已经被开发出来，并用于使用分子和免疫分析来识别与肿瘤进展相关的差异表达基因。促炎症细胞因子、相关信号转导通路分子和即刻早期转录因子基因随着肿瘤的进展而过度表达或激活，并与侵袭性生长和转移有关。这些候选基因在肿瘤过表达或抑制后的功能一直是分子和免疫治疗的潜在靶点研究的主题。基于这些肿瘤产生的细胞因子干扰免疫反应的假设，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反应的激活的研究一直在进行中。第一个用于研究免疫治疗的同基因小鼠口腔癌模型是与路易斯维尔大学的研究人员合作开发的。这些研究已经确定了三种具有抗肿瘤活性的细胞因子。免疫的细胞机制和所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合于人类临床试验。-细胞因子、鳞状细胞癌、白介素类、转录因子、核因子kappaB-人类受试者

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. - cytokines, squamous cell carcinoma, interleukins, transcription factors, nuclear factor kappaB - Human Subjects