TUMOR PROGRESSION AND THE IMMUNOBIOLOGY OF METASTASIS

肿瘤进展和转移的免疫生物学

• 批准号: 3179222
• 负责人: PHILIP FROST
• 金额: $ 9.81万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-01 至 1986-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3179222
• 关键词: autoradiography; cell mediated cytotoxicity; clone cells; gene expression; genetic strain; host neoplasm interaction; immunogenetics; metastasis; monoclonal antibody; neoplasm /cancer genetics; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; neoplasm /cancer invasiveness; neoplasm /cancer transplantation; radiotracer; suppressor T lymphocyte; thymectomy; tumor antigens; tumor promoters

We recently postulated that one mechanism by which tumors progress to a heterogeneous malignant state is via undermethylation of DNA. DNA hypomethylation may result in the expression of genes that were previously not expressed. The treatment of tumor cells with 5-azacytidine has resulted in the selection of clones with varying phenotypes including tumor-immunogenic, nonmetastatic clones from metastatic tumors, metastatic clones from nonmetaststic tumors, and TK+ clones from cell populations that are spontaneously TK-. We continue to investigate the role of under methylation in the generation of the malignant phenotype. The second phase of our study is to assess the usefulness of immunogenic variants in the adoptive immunization of animals bearing metastatic tumors. Our current therapeutic protocol includes surgery, elimination of suppressor cells, adoptive transfer with primed spleen cells, and II-2 administration. These protocols have resulted in considerable prolongation of survival of animals challenged with a tumor considered to be the most aggressive murine tumor known. New experiments will utilize both active and adoptive immunization of animals using both the aggressive tumor and some additional less malignant (metastatic) tumors. Finally, we are also undertaking a series of studies to attempt to identify the antigen expressed by the immunogenic variants using antibodies in the hope of eventually using genetic probes to identify the genes responsible for antigen expression. (IP)

我们最近假设，肿瘤进展为恶性肿瘤的一种机制， 异质恶性状态是通过DNA甲基化不足。 DNA 低甲基化可能导致先前被抑制的基因的表达。 没有表达。 用5-氮杂胞苷治疗肿瘤细胞， 导致选择具有不同表型的克隆，包括 肿瘤免疫原性的，来自转移性肿瘤的非转移性克隆，转移性 来自非增殖性肿瘤的TK+克隆和来自 是自发性TK-。 我们继续调查在 甲基化在恶性表型的产生中的作用。 第二阶段 我们的研究的目的是评估免疫原性变异体在 携带转移性肿瘤的动物的过继免疫。 我们目前 治疗方案包括手术，消除抑制细胞， 用致敏的脾细胞过继转移和II-2给药。 这些 实验方案导致动物的存活时间大大延长， 用被认为是最具侵袭性的鼠肿瘤进行攻击 知道的 新实验将利用主动免疫和过继免疫 同时使用侵袭性肿瘤和一些额外的 恶性（转移性）肿瘤。 最后，我们还开展了一系列 的研究，试图确定抗原表达的免疫原性 希望最终能利用基因探针， 鉴定负责抗原表达的基因。 （IP）