Dadabayev Alisher R, Wang Zhiqing, Zhang Yana, Zhang Jian, Robinson William R, Lim Seah H
Division of Hematology and Oncology, Texas Tech University Health Sciences Center, Amarillo, 79106, USA.
Am J Hematol. 2005 Sep;80(1):6-11. doi: 10.1002/ajh.20415.
Despite advances in chemotherapeutic agents, the prognosis for some cancers remains extremely poor, suggesting the need for other treatment modalities. Immunotherapy appears an ideal approach because the mechanisms of tumor cell killing induced by tumor vaccines are different from those from chemotherapy. Various investigations are ongoing to identify suitable targets for this purpose. Sperm protein 17 (Sp17) was originally identified by our group as a novel cancer-testis antigen in various malignancies, including multiple myeloma. Sp17 is a highly immunogenic protein and the observation that more than 90% of vasectomized males develop immunity against Sp17 suggests the opportunity and safety of Sp17 for tumor vaccines. Recent works by other workers suggest a low level of expression of Sp17 in some normal tissues, and investigators have questioned whether Sp17 is in fact a suitable target for immunotherapy. In this paper, we review the general principles of immunotherapy and provide evidence supporting the highly immunogenic nature of Sp17. We also address the discrepancies between the objectives of oncologists involved in treating cancer patients and their familiarity with acceptable levels of toxicity of any effective therapy and those of pure laboratory-based investigators. Finally, we present some early clinical data supporting the rationale for further investigations of Sp17 for tumor vaccines.
尽管化疗药物取得了进展，但某些癌症的预后仍然极差，这表明需要其他治疗方式。免疫疗法似乎是一种理想的方法，因为肿瘤疫苗诱导的肿瘤细胞杀伤机制与化疗不同。为此，正在进行各种研究以确定合适的靶点。精子蛋白17（Sp17）最初由我们的研究小组鉴定为包括多发性骨髓瘤在内的各种恶性肿瘤中的一种新型癌胚抗原。Sp17是一种高度免疫原性的蛋白质，超过90%接受输精管切除术的男性会产生针对Sp17的免疫力，这表明Sp17用于肿瘤疫苗具有可行性和安全性。其他研究人员最近的工作表明，Sp17在一些正常组织中的表达水平较低，研究人员质疑Sp17是否实际上是免疫治疗的合适靶点。在本文中，我们回顾了免疫治疗的一般原则，并提供了支持Sp17具有高度免疫原性的证据。我们还讨论了参与治疗癌症患者的肿瘤学家的目标与其对任何有效治疗的可接受毒性水平的熟悉程度之间的差异，以及那些纯粹基于实验室的研究人员之间的差异。最后，我们展示了一些早期临床数据，支持进一步研究Sp17用于肿瘤疫苗的理论依据。
