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基于树突状细胞的血液系统恶性肿瘤免疫疗法。

DC-based immunotherapy for hematological malignancies.

作者信息

Kitawaki Toshio

机构信息

Department of Hematology and Oncology, Kyoto University Hospital, 54 Shogoin Kawara-cho, Sakyo-ku, Kyoto, 606-8507, Japan,

出版信息

Int J Hematol. 2014 Feb;99(2):117-22. doi: 10.1007/s12185-013-1496-4. Epub 2013 Dec 31.

Abstract

Great advances have been made in the treatment of hematological malignancies, but achieving a definitive cure remains an elusive goal for the majority of patients. Antigen-specific tumor immunotherapy has the potential to improve clinical outcome in patients with such diseases by eradicating chemotherapy-resistant tumor cell clones without damaging normal tissues. Dendritic cells (DCs) serve as an essential link between the innate and the adaptive immune systems, acting as key controllers of antigen-specific T cell responses. Molecular identification of tumor-specific antigens recognized by T lymphocytes and technical advances in ex vivo generation of human DCs has enabled us to develop DC-based tumor immunotherapies (also called "DC vaccines"). To date, a large number of clinical trials of DC vaccines have been conducted for a variety of tumors, including hematological malignancies. Overall, these trials have demonstrated that DC vaccines have excellent safety profiles, moderate immunological activity, and mild clinical efficacy. To establish a role for DC vaccines in the treatment of hematological malignancies, we need both to define patient populations that can obtain clinical benefit from DC vaccines and to develop combination therapies that augment clinical efficacy of DC vaccines. In this review, I will describe current status of DC-based immunotherapy for hematological malignancies, and discuss future perspectives in this field.

摘要

血液系统恶性肿瘤的治疗已取得了巨大进展,但对大多数患者而言,实现彻底治愈仍是一个难以企及的目标。抗原特异性肿瘤免疫疗法有潜力通过根除化疗耐药的肿瘤细胞克隆而不损害正常组织,来改善此类疾病患者的临床结局。树突状细胞(DC)是先天性免疫系统和适应性免疫系统之间的重要纽带,是抗原特异性T细胞反应的关键调控者。对T淋巴细胞识别的肿瘤特异性抗原进行分子鉴定以及体外培养人DC的技术进步,使我们能够开发基于DC的肿瘤免疫疗法(也称为“DC疫苗”)。迄今为止,已针对包括血液系统恶性肿瘤在内的多种肿瘤开展了大量DC疫苗的临床试验。总体而言,这些试验表明DC疫苗具有良好的安全性、适度的免疫活性和轻微的临床疗效。为确立DC疫苗在血液系统恶性肿瘤治疗中的作用,我们既需要明确能从DC疫苗中获得临床益处的患者群体,也需要开发增强DC疫苗临床疗效的联合疗法。在这篇综述中,我将描述基于DC的血液系统恶性肿瘤免疫疗法的现状,并探讨该领域的未来前景。

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