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树突状细胞在癌症疫苗治疗中的临床应用。

Clinical application of dendritic cells in cancer vaccination therapy.

作者信息

Svane Inge Marie, Soot Mette Line, Buus Søren, Johnsen Hans E

机构信息

Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.

出版信息

APMIS. 2003 Jul-Aug;111(7-8):818-34. doi: 10.1034/j.1600-0463.2003.11107813.x.

Abstract

During the last decade use of dendritic cells (DC) has moved from murine and in vitro studies to clinical trials as adjuvant in cancer immunotherapy. Here they function as delivery vehicles for exogenous tumor antigens, promoting an efficient antigen presentation. The development of protocols for large-scale generation of dendritic cells for clinical applications has made possible phase I/II studies designed to analyze the toxicity, feasibility and efficacy of this approach. In clinical trials, DC-based vaccination of patients with advanced cancer has in many cases led to immunity and in selected patients to tumor regression. However, the majority of clinical trials are still in phase I, and interpretations are hampered by pronounced variation in study design related to technical aspects of DC preparation, treatment and schedule, monitoring of immune response, and clinically relevant endpoints, including toxicity and response evaluation. This paper aims to review the technical aspects and clinical impact of vaccination trials, focusing on the generation of DC-based vaccines, evaluation of immunologic parameters and design of clinical trials necessary to meet the need for good laboratory and clinical practice.

摘要

在过去十年中,树突状细胞(DC)的应用已从鼠类和体外研究转向临床试验,作为癌症免疫治疗的佐剂。在这里,它们作为外源性肿瘤抗原的递送载体,促进有效的抗原呈递。用于临床应用的大规模生成树突状细胞方案的开发,使得旨在分析这种方法的毒性、可行性和疗效的I/II期研究成为可能。在临床试验中,对晚期癌症患者进行基于DC的疫苗接种在许多情况下已导致免疫,在部分患者中还导致肿瘤消退。然而,大多数临床试验仍处于I期,由于在研究设计方面存在明显差异,包括DC制备、治疗和时间表的技术方面、免疫反应监测以及包括毒性和反应评估在内的临床相关终点,使得解释受到阻碍。本文旨在综述疫苗接种试验的技术方面和临床影响,重点关注基于DC的疫苗的生成、免疫参数评估以及满足良好实验室和临床实践需求所需的临床试验设计。

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