Abe J, Wakimoto H, Tsunoda R, Okabe S, Yoshida Y, Aoyagi M, Hirakawa K, Hamada H
Department of Molecular Biotherapy Research, Cancer Institute, Tokyo, Japan.
Biochem Biophys Res Commun. 1996 Jan 5;218(1):164-70. doi: 10.1006/bbrc.1996.0029.
Immunotherapy with adoptive transfer of genetically-modified cytotoxic T lymphocytes (CTL) is a promising approach for cancer gene therapy. We developed an adoptive therapy model with murine tumor-specific CTL, to which very efficient (up to 100%) gene introduction was achieved by using recombinant adenoviral vectors. Through a comparative study on the antitumor effects of CTL genetically modified with cytokine genes, transduction with interferon-gamma gene resulted in a prominent increase in therapeutic efficacy of CTL in both metastatic and subcutaneous tumor models. Further additive effect was obtained by the adoptive cellular therapy in combination with vaccination of cytokine gene-modified tumor cells. Our findings provide a hopeful strategy of adoptive immunotherapy for human cancers.
通过基因改造的细胞毒性T淋巴细胞(CTL)进行过继性转移免疫疗法是一种很有前景的癌症基因治疗方法。我们利用鼠源肿瘤特异性CTL建立了一种过继性治疗模型,通过使用重组腺病毒载体可实现高效(高达100%)的基因导入。通过对用细胞因子基因进行基因改造的CTL的抗肿瘤作用进行比较研究,在转移性和皮下肿瘤模型中,用干扰素-γ基因转导均导致CTL的治疗效果显著提高。通过过继性细胞疗法与细胞因子基因改造的肿瘤细胞疫苗联合使用,可获得进一步的累加效应。我们的研究结果为人类癌症的过继性免疫疗法提供了一种有希望的策略。