Chiriva-Internati Maurizio, Weidanz Jon A, Yu Yuefei, Frezza Eldo E, Jenkins Marjorie R, Kennedy Ronald C, Cobos Everardo, Kast W Martin
Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, Lubbock, TX 79430-6591, USA.
J Immunother. 2008 Oct;31(8):693-703. doi: 10.1097/CJI.0b013e31818283d5.
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.
对于患有晚期或转移性疾病的卵巢癌(OC)患者,标准治疗方法(化疗和放疗)效果不佳且有不良副作用。癌症治疗中更新颖、更有前景的方法是利用免疫系统的组成部分。在本研究中,我们在NOD.CB17-PrkDCcid/J(非肥胖、糖尿病严重联合免疫缺陷)小鼠模型中应用了一种基于过继性免疫疗法的方法,使用癌胚抗原精子蛋白17作为治疗人类转移性OC的靶点。我们使用内源性表达精子蛋白17的人SK-OV-3A2.A3 OC细胞系在小鼠体内诱导肿瘤生长。我们首次提供了直接证据,表明体外培养的、针对精子蛋白17的单克隆细胞毒性T淋巴细胞(源自晚期OC患者或健康供体)能够根除人类转移性OC细胞。此外,在对组织切片进行组织学检查后,我们未观察到自身免疫的迹象,这进一步证明了我们方法的安全性。