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新型免疫疗法。

Novel immunotherapies.

机构信息

Division of Cancer Medicine, Department of Lymphoma and Myeloma, Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

出版信息

Cancer J. 2009 Nov-Dec;15(6):502-10. doi: 10.1097/PPO.0b013e3181c51f0d.

Abstract

Multiple myeloma is still a fatal disease. Despite advances in high-dose chemotherapy and stem-cell transplantation and the development of novel therapeutics, relapse of the underlying disease remains the primary cause of treatment failure. Strategies for posttransplantation immunomodulation are desirable for eradication of remaining tumor cells. To this end, immunotherapy aimed at inducing myeloma-specific immunity in patients has been explored. Idiotype protein, secreted by myeloma cells, has been the primary target for immunotherapy as it is the best defined tumor-specific antigen. This chapter focuses on novel immunotherapies that are being developed to treat patients with myeloma. I will discuss potential myeloma antigens, antigen-specific T cells, and their function on myeloma tumor cells, and T-cell-based and antibody-based immunotherapies for myeloma. Furthermore, clinical studies of T-cell-based immunotherapy in the form of vaccination, allogeneic stem-cell transplantation and donor lymphocyte infusions, with or without donor vaccination using patient-derived idiotype, and future application of donor-derived or patient-derived, antigen-specific T-cell infusion in this disease are also discussed. Based on the specificity of the immune effector molecules and cells, immunotherapies with specific T cells or therapeutic antibodies may represent novel strategies for the treatment of multiple myeloma in the near future.

摘要

多发性骨髓瘤仍然是一种致命的疾病。尽管大剂量化疗和干细胞移植的进展以及新型治疗方法的发展,基础疾病的复发仍然是治疗失败的主要原因。为了根除残留的肿瘤细胞,需要进行移植后的免疫调节策略。为此,已经探索了针对诱导患者骨髓瘤特异性免疫的免疫疗法。骨髓瘤细胞分泌的独特型蛋白一直是免疫治疗的主要靶点,因为它是定义最明确的肿瘤特异性抗原。本章重点介绍正在开发用于治疗骨髓瘤患者的新型免疫疗法。我将讨论潜在的骨髓瘤抗原、抗原特异性 T 细胞及其对骨髓瘤肿瘤细胞的功能,以及基于 T 细胞和抗体的骨髓瘤免疫疗法。此外,还讨论了使用患者来源的独特型对供体进行疫苗接种、同种异体干细胞移植和供体淋巴细胞输注的 T 细胞为基础的免疫疗法的临床研究,以及未来在这种疾病中使用供体或患者来源的、抗原特异性 T 细胞输注的应用。基于免疫效应分子和细胞的特异性,针对特定 T 细胞或治疗性抗体的免疫疗法可能代表了治疗多发性骨髓瘤的新策略,有望在不久的将来得到应用。

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