Batich Kristen A, Swartz Adam M, Sampson John H
Duke Brain Tumor Immunotherapy Program, Division of Neurosurgery, Department of Surgery ; Durham, NC 27710 , USA.
Expert Opin Biol Ther. 2015 Jan;15(1):79-94. doi: 10.1517/14712598.2015.972361. Epub 2014 Oct 18.
Patients with primary glioblastoma (GBM) have a dismal prognosis despite standard therapy, which can induce potentially deleterious side effects. Arming the immune system is an alternative therapeutic approach, as its cellular effectors and inherent capacity for memory can be utilized to specifically target invasive tumor cells, while sparing collateral damage to otherwise healthy brain parenchyma.
Active immunotherapy is aimed at eliciting a specific immune response against tumor antigens. Dendritic cells (DCs) are one of the most potent activators of de novo and recall immune responses and are thus a vehicle for successful immunotherapy. Currently, investigators are optimizing DC vaccines by enhancing maturation status and migratory potential to induce more potent antitumor responses. An update on the most recent DC immunotherapy trials is provided.
Targeting of unique antigens restricted to the tumor itself is the most important parameter in advancing DC vaccines. In order to overcome intrinsic mechanisms of immune evasion observed in GBM, the future of DC-based therapy lies in a multi-antigenic vaccine approach. Successful targeting of multiple antigens will require a comprehensive understanding of all immunologically relevant oncological epitopes present in each tumor, thereby permitting a rational vaccine design.
原发性胶质母细胞瘤(GBM)患者尽管接受了标准治疗,但其预后仍然很差,而且标准治疗可能会引发潜在的有害副作用。增强免疫系统是一种替代治疗方法,因为其细胞效应器和固有的记忆能力可用于特异性靶向侵袭性肿瘤细胞,同时避免对其他健康脑实质造成附带损害。
主动免疫疗法旨在引发针对肿瘤抗原的特异性免疫反应。树突状细胞(DC)是从头免疫反应和回忆免疫反应最有效的激活剂之一,因此是成功进行免疫治疗的载体。目前,研究人员正在通过提高成熟状态和迁移潜力来优化DC疫苗,以诱导更强有力的抗肿瘤反应。本文提供了最新DC免疫治疗试验的相关信息。
靶向仅限于肿瘤本身的独特抗原是推进DC疫苗的最重要参数。为了克服GBM中观察到的免疫逃逸内在机制,基于DC的治疗的未来在于多抗原疫苗方法。成功靶向多种抗原将需要全面了解每个肿瘤中存在的所有与免疫相关的肿瘤表位,从而实现合理的疫苗设计。