GENERATION OF TUMOR INFILTRATING LYMPHOCYTES (TIL) FROM HHV-6 DNA INDUCED TUMORS

HHV-6 DNA 诱导肿瘤产生肿瘤浸润淋巴细胞 (TIL)

• 批准号: 3811250
• 负责人: A RAZZAQUE
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3811250
• 关键词: DNA; athymic mouse; cellular oncology; cytogenetics; cytotoxic T lymphocyte; gene expression; genome; neoplasm /cancer genetics; neoplastic transformation; nucleic acid structure; tissue /cell culture; transfection

We have recently shown that the HHV-6 genome and a subgenomic clone, pZVHI4, can morphologically transform NIH 3T3 cells which can produce tumors in nude mice. In this project, we also observed that these tumorigenic cells could produce tumors in immunocompetent mice and metastasize to the lung. The tumors induced by the entire HHV-6 genome and the subgenomic clone, pZVHI4, were designated as G-2TS and l4-2TS, respectively. We have generated TIL from these tumors and expanded them in culture with recombinant IL-2. These TIL lysed various targets in (51)Cr-release assays. TIL derived from G-2TS tumors lysed specifically its autologous targets and maintained their specificity over 6-month period. However, at the early phase of culture, TIL derived from l4-2TS tumors lysed autologous tumors as well as allogeneic targets including Yac-1 lymphoma. After several days in culture, these l4-2TS TIL lost their lytic capability of autologous targets, but continued to lyse Yac-I target even after 56 days of culture. Phenotypically, these TIL were Thy 1.2+, Lyt-2+ and L3T4-. These studies indicate that HHV-6 DNA transfected NIH 3T3 cells acquire both tumorigenic and metastatic potential and tumor bearing hosts can mount immune responses against such tumors.

我们最近展示了HHV-6基因组和亚基因组克隆，