IMMUNOTHERAPY OF MELANOMA WITH LYMPH NODE PRIMED WITH GMCSF GENE TRANSDUCED CELL

密歇根大学的研究人员在通过将编码移植抗原的外来基因直接接种到肿瘤内来治疗肿瘤的研究中走在了前列。在最初的临床研究中，将这种复合体与脂质体一起接种到肿瘤内，可以引起肿瘤内的炎症反应，肿瘤细胞上异体移植抗原的表达，肿瘤内T淋巴细胞的渗透，以及在一小部分患者中注射的结节消退。这些初步研究还表明，治疗前和治疗后相比，从肿瘤中提取的TIL细胞识别和响应肿瘤抗原的能力增强。在这个方案中，我们建议将人类白细胞抗原-B7基因复合体与脂质体一起注射到黑色素瘤中，然后将其切除以产生肿瘤浸润性淋巴细胞(TIL)。在TIL的临床前和临床研究中，TIL细胞的输注已导致已建立的晚期肿瘤负担的消退。这种形式的治疗被称为过继治疗。据推测，外源MHC基因的表达导致肿瘤内的炎症环境，从而增强了浸润性T细胞对肿瘤抗原的敏感性。在这些初步研究的基础上，我们启动了这一临床方案，以确定从人类白细胞抗原-B7转基因肿瘤中产生TIL用于后续过继免疫治疗的可行性。将对TIL进行进一步的研究，以评估它们在基因转移前后的免疫功能。

University of Michigan researchers have been in the forefront in the investigation of treating tumors by the direct intratumoral inoculation of a foreign gene encoding a transplantation antigen known as, HLA-B7. In initial clinical studies, the intratumoral inoculation of this complex with liposomes induces an inflammatory response within the tumor, expression of the foreign transplantation antigen on tumor cells, infiltration of T lymphocytes within the tumor; and, regression of the injected nodules in a small subgroup of patients. These preliminary studies also demonstrated that the TIL extracted from the tumor prior to treatment and compared to post treatment demonstrated enhanced ability of the TIL cells to recognize and respond to tumor antigen. In this protocol, we propose to administer HLA-B7 gene complex with liposomes into melanoma tumors which will subsequently be excised for the generation of tumor infiltrating lymphocytes (TIL). In pre-clinical and clinical studies of TIL, the infusion of TIL cells has resulted in the regression of established, advanced tumor burdens. This form of therapy is known as adoptive therapy. It is hypothesized that the expression of the foreign MHC gene results in an inflammatory milieu within the tumor which allows enhanced sensitization of infiltrating T cells to respond to tumor antigens. Based on these preliminary studies, we have initiated this clinical protocol to determine the feasibility of generating TIL derived from HLA-B7 transfected tumors for subsequent adoptive immunotherapy. Additional studies will be performed on the TIL to evaluate their immunological function both pre and post gene transfer.