Sperm protein 17 is a suitable target for adoptive T-cell-based immunotherapy in human ovarian cancer

Sperm protein 17 is a suitable target for adoptive T-cell-based immunotherapy in human ovarian cancer
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DOI:
10.1097/cji.0b013e31818283d5
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发表时间:
2008-10-01
影响因子:
3.9
通讯作者:
Kast, W. Martin
Kast, W. Martin
中科院分区:
医学4区
文献类型:
--
作者:
Chiriva-Internati, Maurizio;Weidanz, Jon A.;Kast, W. Martin

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对于患有晚期或转移性疾病的卵巢癌(OC)患者,标准治疗(化疗和放疗)不是很有效,并且具有不良副作用。癌症治疗中更新和更有前途的方法使用免疫系统的组成部分。在这项研究中,我们采用了过继免疫治疗为基础的方法,使用癌症睾丸抗原,精子蛋白17,作为一个目标,用于治疗人类转移性OC的NOD.CB17-PrkDCcid/J(非肥胖,糖尿病严重联合免疫缺陷)小鼠模型。我们使用内源性表达精子蛋白17的人SK-OV-3A2.A3 OC细胞系诱导小鼠肿瘤生长。我们首次提供了直接证据,证明体外培养的单克隆细胞毒性T淋巴细胞(来自晚期OC患者或健康供体),特异于精子蛋白17,可以根除人类转移性OC细胞。此外,在组织切片的组织学检查后,我们没有观察到自身免疫的证据,这增加了我们方法的安全性。
For ovarian cancer (OC) patients with advanced or metastatic disease, standard treatments (chemotherapy and radiotherapy) are not very effective and have undesirable side effects. Newer and more promising approaches in cancer treatment use components of the immune system. In this study, we applied an adoptive immunotherapy-based approach using a cancer testis antigen, sperm protein 17, as a target for the treatment of human metastatic OC in a NOD.CB17-PrkDCcid/J (nonobese, diabetic severe combined immunodeficient) mouse model. We used the human SK-OV-3A2.A3 OC cell line, endogenously expressing sperm protein 17, to induce tumor growth in mice. We provide direct evidence, for the first time, that in vitro cultured, monoclonal, cytotoxic T lymphocytes (derived either from advanced OC patients or from healthy donors), specific for sperm protein 17, can eradicate human metastatic OC cells. In addition, we observed no evidence of autoimmunity after histologic examination of the tissue sections adding to the safety profile of our approach.