MUTAGE/UV INDUCED IMMUNE VARIANTS IN METASTASIS THERAPY

转移治疗中突变/紫外线诱导的免疫变异

• 批准号: 3182105
• 负责人: PHILIP FROST
• 金额: $ 13.89万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1990-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3182105
• 关键词: T lymphocyte; active immunization; cancer registry /resource; clone cells; combination cancer therapy; cyclophosphamide; disease /disorder model; interleukin 2; laboratory mouse; leukocyte activation /transformation; macrophage activating factor; metastasis; model design /development; mutagens; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; neoplastic cell; suppressor T lymphocyte; ultraviolet radiation

Our purpose is to make use of a novel means of generating immunogenic tumor variants for the immunotherapy of metastasis. The animal model described is one which attempts to mimic the clinical situation, where metastasis is the major cause of death. Our protocols include surgical removal of the primary tumor followed by treatment with cyclophosphamide to inhibit putative suppressor T cells. This is followed by adoptive immunization with syngeneic lymphocytes activated with immunogenic clones derived from the parent tumor by mutagen or UV light treatment. These immunogenic clones generate allogeneic-like cytotoxic T cell responses which protect against parent tumor challenge in vivo. Preliminary data have demonstrated that adoptive immunotherapy can 'cure' as many as 60% of animals bearing one of the most aggressive metastatic murine tumors known. In addition, we have early evidence that active immunization of animals with established metastasis with viable immunogenic clones, may also be an effective therapeutic modality. We plan to further assess the use of IL-2 in combination with adoptive or active immunotherapy for the treatment of established metastasis, an attempt will also be made to assess the usefullness of adoptive and/or active immunization in conjunction with non-specific macrophage activation using MTP-PE. Experiments designed to define at least in part, the nature of the mutagen or UV induced antigen will also be performed.

我们的目的是利用一种新的方法来产生 免疫原性肿瘤变异体在免疫治疗中的应用 转移。所描述的动物模型是一个试图 为了模拟临床情况，其中转移是主要的 死因是。我们的治疗方案包括手术切除 原发肿瘤继发环磷酰胺治疗 抑制可能的抑制性T细胞。这之后是 同种异体淋巴细胞的过继免疫 通过诱变剂或诱变剂从亲本肿瘤获得的免疫原性克隆 紫外线治疗。这些免疫原性克隆产生 同种异体样细胞毒性T细胞反应保护 体内对抗亲本肿瘤的挑战。初步数据显示 证明过继免疫疗法可以治愈多达 60%的动物携带最具侵袭性的转移瘤之一 已知的小鼠肿瘤。此外，我们有初步证据表明 对已确定转移的动物进行主动免疫 活的免疫原性克隆，也可能是一种有效的治疗方法 情态。我们计划进一步评估IL-2在 联合过继或主动免疫治疗 治疗已确立的转移，也将是一种尝试 用于评估收养和/或主动收养的有用性 与非特异性巨噬细胞联合免疫 使用MTP-PE激活。实验旨在定义 至少部分原因是诱变剂或紫外线诱导的抗原的性质 也将上演。