TRANSFECTANT INFLUENZA VIRUSES IN CANCER THERAPY

描述：(申请人摘要)最近，不同的肿瘤相关 肿瘤浸润性肿瘤识别的抗原(TAA) 淋巴细胞已经被鉴定出来。癌症治疗的成功可能会 依赖于诱导有效的细胞免疫反应来对抗TAAs。 一种非常有希望的治疗肿瘤的方法包括使用重组 表达所需TAA的病毒载体，因为大多数病毒能够 诱导强烈而持久的免疫反应，对抗其表达的 抗原。早些时候有研究表明，转基因流感病毒载体 可以诱导强大的细胞免疫反应来对抗表达的 小鼠体内的抗原，特别是当它们与 表达相同抗原的重组痘苗病毒。在这 应用：转基因疫苗诱导的抗肿瘤免疫应答 表达TAA模型的流感病毒将在小鼠身上进行分析。小说 免疫方案，包括使用两种不同的病毒载体 为了诱导强大的抗肿瘤细胞免疫反应，将进行研究。在……里面 此外，实验的重点是提高转基因的安全性 流感病毒也被设计出来了。顺式作用RNA的影响 病毒中流感病毒基因表达调控的序列 致病性和免疫原性将被确定。稳定衰减 表达小鼠TAA模型的转基因流感病毒将被 并将对其抗肿瘤特性进行表征。最后， 表达人肿瘤相关抗原的流感病毒载体 黑色素瘤将被构建为未来可能用于人类的肿瘤。这个 感染这些病毒的细胞的能力 对肿瘤所识别的浸润性淋巴细胞进行分析。建议数 研究可能会推动癌症治疗领域朝着可能的新方法发展 治疗人类肿瘤，延长癌症患者的生存时间。

DESCRIPTION: (Applicant's Abstract) Recently, different tumor associated antigens (TAAs) which are capable of being recognized by tumor infiltrating lymphocytes have been identified. The success of cancer therapies may depend on the induction of effective cellular immune responses against TAAs. A very promising approach to treat tumors involves the use of recombinant viral vectors expressing the desired TAAs, since most viruses are able to elicit strong and long-lasting immune responses against their expressed antigens. Earlier it was shown that transfectant influenza virus vectors could induce powerful cellular immune responses against the expressed antigens in mice, especially when they were administered in combination with recombinant vaccinia viruses expressing the same antigen. In this application, the antitumor immune responses elicited by transfectant influenza viruses expressing a model TAA will be analyzed in mice. Novel protocols of immunization, including the use of two different viral vectors to induce powerful antitumor cellular immune responses, will be studied. In addition, experiments focused on improving the safety of the transfectant influenza viruses have also been designed. The influence of cis-acting RNA sequences in the regulation of influenza virus gene expression, in viral pathogenicity, and immunogenicity will be determined. Stably attenuated transfectant influenza viruses expressing a model murine TAA will be engineered and their antitumor properties will be characterized. Finally, influenza virus vectors expressing human tumor associated antigens from melanoma tumors will be constructed for possible future use in humans. The ability of cells which have been infected with these viruses to be recognized by tumor infiltrating lymphocytes will be analyzed. The proposed research may advance the field of cancer therapy towards possible novel ways to treat human tumors and prolong survival of cancer patients.