Cornetta K, Berebitsky D, Behnia M, Traycoff C, Srour E F, Sledge G W
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202, USA.
Cancer Gene Ther. 1994 Jun;1(2):91-8.
The use of cytokines to modify antigen expression on syngeneic murine tumor cells has led to immunization of the host from subsequent challenges with the parent tumor cell line. To determine whether this approach can be applied to human malignancies we introduced the human interferon gamma gene (IFN gamma) into the human breast cancer cell lines MDA-MB-435 and MDA-MB-231 using retroviral-mediated gene transfer. Retroviral transfer of the IFN gamma gene was associated with decreased growth, decreased tumor invasiveness, IFN gamma production, and upregulation of MHC antigens. While the MDA-MB-435 produced higher levels of IFN gamma than MDA-MB-231, MHC class I and class II antigens were upregulated in both cell lines. Introduction of this vector into the human leukemia cell line K562 led to increased expression of MHC class I antigens, but not class II. Our findings suggest that expression of interferon gamma in breast cancer cells may lead to increased recognition of breast cancer cells by the host immune system. Furthermore, these data suggest that further development of this approach to cancer immunotherapy is warranted.
利用细胞因子改变同基因小鼠肿瘤细胞上的抗原表达，已使宿主对随后来自亲本肿瘤细胞系的攻击产生免疫。为了确定这种方法是否可应用于人类恶性肿瘤，我们使用逆转录病毒介导的基因转移，将人干扰素γ基因（IFNγ）导入人乳腺癌细胞系MDA-MB-435和MDA-MB-231。IFNγ基因的逆转录病毒转移与生长减慢、肿瘤侵袭性降低、IFNγ产生以及MHC抗原上调有关。虽然MDA-MB-435产生的IFNγ水平高于MDA-MB-231，但两种细胞系中MHC I类和II类抗原均上调。将该载体导入人白血病细胞系K562导致MHC I类抗原表达增加，但II类抗原未增加。我们的研究结果表明，乳腺癌细胞中干扰素γ的表达可能导致宿主免疫系统对乳腺癌细胞的识别增加。此外，这些数据表明，这种癌症免疫治疗方法值得进一步开发。
