Todryk S M, Chong H, Vile R G, Pandha H, Lemoine N R
Laboratory of Molecular Therapy, Imperial Cancer Research Fund Molecular Oncology Unit, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, UK.
Gut. 1998 Oct;43(4):445-9. doi: 10.1136/gut.43.4.445.
Gene therapy, in particular the transfer of genes encoding immunostimulatory molecules (cytokines and costimulatory molecules) as well as selectively cytotoxic enzymes and DNA vaccination, has the potential of enhancing cell mediated immune responses against tumours including those of colorectal origin. Genes can be transferred using viral vectors either to cultured tumour cells in vitro that can be returned to the patient as a "cancer vaccine", or directly to tumour cells in vivo. Vaccination with DNA constructs expressing specific tumour antigens characteristic of colorectal neoplasia can trigger immune recognition and destruction of tumour cells. The aim is to tip the balance from protumour to antitumour mechanisms by generating a local immune response and systemic antitumour immune memory to destroy metastases. Studies in murine models, combined with human studies, show that such approaches could become an adjunct to current treatments for human colorectal cancer in the near future.
基因治疗,特别是编码免疫刺激分子(细胞因子和共刺激分子)的基因转移,以及选择性细胞毒性酶和DNA疫苗接种,有可能增强针对包括结直肠癌起源肿瘤在内的肿瘤的细胞介导免疫反应。基因可以使用病毒载体转移到体外培养的肿瘤细胞中,这些细胞可以作为“癌症疫苗”返回给患者,或者直接在体内转移到肿瘤细胞中。用表达结直肠肿瘤特征性特定肿瘤抗原的DNA构建体进行疫苗接种可以触发肿瘤细胞的免疫识别和破坏。目的是通过产生局部免疫反应和全身抗肿瘤免疫记忆来破坏转移灶,从而将平衡从促肿瘤机制转向抗肿瘤机制。在小鼠模型中的研究以及人体研究表明,这些方法在不久的将来可能成为人类结直肠癌当前治疗的辅助手段。