MUTAGE/UV INDUCED IMMUNE VARIANTS IN METASTASIS THERAPY

我们的目的是利用一种新的方法 用于免疫治疗的免疫原性肿瘤变体 转移 所描述的动物模型是试图 以模拟临床情况，其中转移是主要的 死因了 我们的方案包括手术切除 原发性肿瘤，然后用环磷酰胺治疗， 抑制假定的抑制性T细胞。 这之后是 用活化的同基因淋巴细胞过继免疫 通过诱变剂从母体肿瘤衍生的免疫原性克隆，或 UV光处理。 这些免疫原性克隆产生 同种异体样细胞毒性T细胞反应， 对抗体内亲本肿瘤攻击。 初步数据 研究表明，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性肿瘤之一， 已知的小鼠肿瘤。 此外，我们有早期证据表明， 对已确定转移的动物进行主动免疫， 可行的免疫原性克隆，也可能是一种有效的治疗方法， 模态 我们计划进一步评估IL-2在 与过继性或主动免疫疗法联合治疗 治疗已建立的转移，也将尝试 用于评估收养和/或主动 与非特异性巨噬细胞联合免疫 使用MTP-PE活化。 实验旨在定义在 至少部分地，诱变剂或UV诱导抗原的性质 也将被执行。

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.