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电化学疗法联合分泌白细胞介素-2的组织不相容细胞的全身抗肿瘤作用

Systemic antitumor effects of electrochemotherapy combined with histoincompatible cells secreting interleukin-2.

作者信息

Mir L M, Roth C, Orlowski S, Quintin-Colonna F, Fradelizi D, Belehradek J, Kourilsky P

机构信息

Laboratoire de Pharmacologie Moléculaire, URA 147 CNRS, Institut Gustave-Roussy, Villejuif, France.

出版信息

J Immunother Emphasis Tumor Immunol. 1995 Jan;17(1):30-8. doi: 10.1097/00002371-199501000-00004.

DOI:10.1097/00002371-199501000-00004
PMID:7537154
Abstract

Electrochemotherapy is an antitumor treatment that combines a cytotoxic drug with the local administration of electric pulses delivered at the tumor site. We previously found that in mice the cure rate of subcutaneous transplanted tumors treated by electrochemotherapy is increased by repeated systemic interleukin-2 (IL-2) injections. Moreover, histoincompatible cells engineered to secrete IL-2 allow the rejection of syngeneic tumor cells when both cells are inoculated together. In this study of preestablished tumors in mice we show that after electrochemotherapy, delayed peritumoral injections of histoincompatible IL-2-producing cells result in the cure of almost all the tumors. Moreover, this combined local treatment leads to cures of untreated, contralaterally transplanted tumors. This systemic antitumor immunity also resulted in complete protection of the cured mice against further inocula of the tumor cells. These results, which were obtained using allogeneic as well as xenogeneic IL-2-secreting cells, suggest that electrochemotherapy combined with such cellular immunotherapy might be a useful approach for the treatment of metastasizing cancers.

摘要

电化学疗法是一种抗肿瘤治疗方法,它将细胞毒性药物与在肿瘤部位施加的局部电脉冲相结合。我们之前发现,在小鼠中,通过重复全身注射白细胞介素-2(IL-2)可提高电化学疗法治疗皮下移植肿瘤的治愈率。此外,经基因工程改造以分泌IL-2的组织不相容细胞,在与同基因肿瘤细胞一起接种时,可使同基因肿瘤细胞被排斥。在这项针对小鼠已建立肿瘤的研究中,我们发现,在电化学疗法后,延迟在肿瘤周围注射组织不相容的产IL-2细胞可使几乎所有肿瘤治愈。此外,这种联合局部治疗可使未治疗的对侧移植肿瘤治愈。这种全身抗肿瘤免疫还使治愈的小鼠完全免受肿瘤细胞再次接种的影响。这些使用同种异体以及异种分泌IL-2细胞获得的结果表明,电化学疗法联合这种细胞免疫疗法可能是治疗转移性癌症的一种有用方法。

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