Immunotherapy of malignancy by in vivo gene transfer into tumors.
Immunotherapy of malignancy by in vivo gene transfer into tumors.
复制标题
通过体内基因转移到肿瘤中进行恶性肿瘤的免疫治疗。
DOI：
10.1073/pnas.90.10.4645
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发表时间：
1993
影响因子：
11.1
通讯作者：
Nabel,GJ
中科院分区：
文献类型：
--
作者：
Plautz,GE;Yang,ZY;Wu,BY;Gao,X;Huang,L;Nabel,GJ
免疫系统对多种病原体提供保护，并有助于监视和破坏肿瘤细胞。多种细胞类型参与肿瘤的识别和溶解，适当的免疫刺激对恶性肿瘤有治疗作用。外源主要组织相容性复合体（MHC）蛋白也可作为免疫系统的有力刺激。在本报告中，一个外源MHC基因被直接引入体内恶性肿瘤，试图刺激肿瘤排斥反应。与以往通过细胞介导的基因转移诱导肿瘤免疫的尝试不同，重组基因在体内直接导入肿瘤。小鼠I类H-2Ks基因在CT26小鼠结肠腺癌（H-2Kd）或MCA 106纤维肉瘤（H-2Kb）中的表达诱导细胞毒性t细胞对H-2Ks的反应，更重要的是，对存在于未修饰肿瘤细胞上的其他抗原的反应。在许多病例中，这种免疫反应减弱了肿瘤的生长，并导致肿瘤完全消退。因此，体内的直接基因转移可以诱导针对特定基因产物的细胞介导免疫，从而为恶性肿瘤提供免疫治疗效果，并有可能应用于人类癌症和传染病的治疗。
The immune system confers protection against a variety of pathogens and contributes to the surveillance and destruction of neoplastic cells. Several cell types participate in the recognition and lysis of tumors, and appropriate immune stimulation provides therapeutic effects in malignancy. Foreign major histocompatibility complex (MHC) proteins also serve as a potent stimulus to the immune system. In this report, a foreign MHC gene was introduced directly into malignant tumors in vivo in an effort to stimulate tumor rejection. In contrast to previous attempts to induce tumor immunity by cell-mediated gene transfer, the recombinant gene was introduced directly into tumors in vivo. Expression of the murine class I H-2Ks gene within the CT26 mouse colon adenocarcinoma (H-2Kd) or the MCA 106 fibrosarcoma (H-2Kb) induced a cytotoxic T-cell response to H-2Ks and, more importantly, to other antigens present on unmodified tumor cells. This immune response attenuated tumor growth and caused complete tumor regression in many cases. Direct gene transfer in vivo can therefore induce cell-mediated immunity against specific gene products, which provides an immunotherapeutic effect for malignancy, and potentially can be applied to the treatment of cancer and infectious diseases in man.