Division of Clinical Immunology & Transfusion Medicine, Department of Laboratory Medicine, Karolinska University Hospital Huddinge F79, Stockholm, Sweden.
Immunotherapy. 2009 May;1(3):483-93. doi: 10.2217/imt.09.13.
Explorative knowledge of cellular and molecular mechanisms of immune function and regulation has provided optimism in developing cancer immunotherapy. However, three decades of experimental and clinical investigations to offer powerful immunotherapeutic strategies against solid tumors, with the possible exception of monoclonal antibody-targeted therapies, have not succeeded in significantly prolonging patient survival. Nonspecific immune approaches, including cytokine-based therapies and allogeneic hematopoietic stem cell transplantation, have so far produced consistent, although limited, results. In this review, we present the developments of cell transfer-based strategies that, in preclinical studies, have demonstrated potential efficacy, but have only established tumor regression in limited numbers of patients. The key to success demands creative combinations of tumor antigens, adjuvance, gene modification and various administration strategies in the development of cell-based therapies together with other cancer-treatment principles, often in a stepwise 'space-rocket-type' approach. Combined efforts of several scientific disciplines, such as tumor biology and immunology, as well as cell and gene research in transplantation, will open new venues. New regulation for clinical trials with advanced therapy medicine products to ensure patient safety will be highlighted.
对免疫功能和调节的细胞和分子机制的探索性了解为开发癌症免疫疗法提供了乐观前景。然而,经过三十年的实验和临床研究,提供针对实体瘤的强大免疫治疗策略,除了单克隆抗体靶向治疗外,并没有成功显著延长患者的生存时间。非特异性免疫方法,包括细胞因子为基础的治疗和同种异体造血干细胞移植,迄今为止已经产生了一致的,尽管是有限的结果。在这篇综述中,我们介绍了基于细胞转移的策略的发展,这些策略在临床前研究中已经证明了潜在的疗效,但只在有限数量的患者中建立了肿瘤消退。成功的关键要求在开发细胞疗法时,创造性地结合肿瘤抗原、佐剂、基因修饰和各种给药策略,以及其他癌症治疗原则,通常采用逐步的“火箭式”方法。肿瘤生物学和免疫学以及移植中的细胞和基因研究等多个科学学科的共同努力将开辟新的途径。将强调用于确保患者安全的高级治疗药物产品临床试验的新法规。