Blaese R M, Mullen C A, Ramsey W J
Cellular Immunology Section, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Pathol Biol (Paris). 1993 Oct;41(8):672-6.
The use of retroviral-mediated gene transfer to introduce a DNA label into T cells (TIL) being used in the immunotherapy of patients with malignant melanoma finally opened the door to the clinical application of gene therapy for a wide variety of inherited and acquired diseases. The gene therapy trial for ADA deficiency SCID has demonstrated that long term stable expression of exogenous genes can be achieved in human T lymphocytes using retroviral vectors for ex vivo treatment and that significant immune reconstitution can be achieved in these patients following periodic infusions with ADA gene-corrected autologous T cells. Newer clinical applications include the insertion of genes into CD34 enriched stem cell populations, the testing of autologous tumor vaccines employing cytokine gene-modified tumor cells and the direct transfer of the herpes thymidine kinase gene into brain tumors in situ in order to render those tumors sensitive to treatment with the ordinarily non-cytotoxic drug ganciclovir.
利用逆转录病毒介导的基因转移将DNA标记引入用于恶性黑色素瘤患者免疫治疗的T细胞（肿瘤浸润淋巴细胞），最终为基因治疗在多种遗传性和获得性疾病中的临床应用打开了大门。针对腺苷脱氨酶缺乏的重症联合免疫缺陷病的基因治疗试验表明，使用逆转录病毒载体进行体外治疗可使人T淋巴细胞实现外源基因的长期稳定表达，并且在这些患者中定期输注经腺苷基因校正的自体T细胞后可实现显著的免疫重建。新的临床应用包括将基因插入富含CD34的干细胞群体、测试采用细胞因子基因修饰肿瘤细胞的自体肿瘤疫苗，以及将疱疹胸苷激酶基因直接原位转移至脑肿瘤，以使这些肿瘤对通常无细胞毒性的药物更昔洛韦治疗敏感。
