Rosenberg S A, Anderson W F, Blaese M, Hwu P, Yannelli J R, Yang J C, Topalian S L, Schwartzentruber D J, Weber J S, Ettinghausen S E
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Ann Surg. 1993 Oct;218(4):455-63; discussion 463-4. doi: 10.1097/00000658-199310000-00006.
The authors sought to develop new treatments for patients with cancer based on the genetic modification of immune lymphocytes and tumor cells designed to increase the host immune reaction against growing cancers.
Retroviral-mediated gene transduction was used to introduce genes into tumor-infiltrating lymphocytes (TIL), and these genetically altered TIL were administered to patients with cancer. Genes coding for cytokines were introduced into tumor cells, and these cells were used to immunize patients against their autologous cancers.
In initial studies, the gene for neomycin phosphotransferase was introduced into the TIL of ten patients with advanced cancer to study the survival and distribution of TIL in humans. These studies showed that retroviral gene transduction is a safe and practical method for adding genes to human cells and led to clinical trials in which the gene for tumor necrosis factor (TNF) was inserted into TIL in an effort to increase their therapeutic effectiveness. Phase I trials are currently underway using TIL that secrete up to 100 times the normal level of TNF. More recently, animal experiments have revealed that transduction of tumor cells with cytokine genes can enhance tumor immunogenicity and, thus, increase the recognition of the tumor as foreign by the host. Clinical trials based on these observations have begun in which patients are immunized against their own autologous tumors that were transduced with the genes for TNF or interleukin-2.
Attempts at gene therapy for cancer are underway and have opened new possibilities for the development of cancer treatments.
作者试图基于对免疫淋巴细胞和肿瘤细胞进行基因改造来开发针对癌症患者的新疗法，旨在增强宿主对生长中的癌症的免疫反应。
采用逆转录病毒介导的基因转导将基因导入肿瘤浸润淋巴细胞（TIL），然后将这些基因改变的TIL给予癌症患者。将编码细胞因子的基因导入肿瘤细胞，并用这些细胞对患者进行自身癌症免疫。
在初步研究中，将新霉素磷酸转移酶基因导入10例晚期癌症患者的TIL中，以研究TIL在人体内的存活和分布情况。这些研究表明，逆转录病毒基因转导是一种向人类细胞添加基因的安全实用方法，并促成了临床试验，在该试验中，将肿瘤坏死因子（TNF）基因插入TIL中以提高其治疗效果。目前正在进行I期试验，使用分泌量高达正常水平100倍TNF的TIL。最近，动物实验表明，用细胞因子基因转导肿瘤细胞可增强肿瘤免疫原性，从而增加宿主将肿瘤识别为异物的能力。基于这些观察结果的临床试验已经开始，让患者对自身经TNF或白细胞介素-2基因转导的自体肿瘤进行免疫。
癌症基因治疗的尝试正在进行中，并为癌症治疗的发展开辟了新的可能性。
