Gustave Roussy; Villejuif, France ; INSERM, U848; Villejuif, France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers; Paris, France ; Université Paris-Sud/Paris XI; Paris, France.
Gustave Roussy; Villejuif, France.
Oncoimmunology. 2014 Jan 1;3(1):e28185. doi: 10.4161/onci.28185. Epub 2014 Apr 1.
During the past 2 decades, the possibility that preparations capable of eliciting tumor-specific immune responses would mediate robust therapeutic effects in cancer patients has received renovated interest. In this context, several approaches to vaccinate cancer patients against their own malignancies have been conceived, including the administration of DNA constructs coding for one or more tumor-associated antigens (TAAs). Such DNA-based vaccines conceptually differ from other types of gene therapy in that they are not devised to directly kill cancer cells or sensitize them to the cytotoxic activity of a drug, but rather to elicit a tumor-specific immune response. In spite of an intense wave of preclinical development, the introduction of this immunotherapeutic paradigm into the clinical practice is facing difficulties. Indeed, while most DNA-based anticancer vaccines are well tolerated by cancer patients, they often fail to generate therapeutically relevant clinical responses. In this Trial Watch, we discuss the latest advances on the use of DNA-based vaccines in cancer therapy, discussing the literature that has been produced around this topic during the last 13 months as well as clinical studies that have been launched in the same time frame to assess the actual therapeutic potential of this intervention.
在过去的 20 年中，人们重新产生了兴趣，认为能够引发肿瘤特异性免疫反应的制剂可能会在癌症患者中产生强大的治疗效果。在这种情况下，已经设想了几种针对癌症患者自身恶性肿瘤的疫苗接种方法，包括给予编码一种或多种肿瘤相关抗原（TAA）的 DNA 构建体。这种基于 DNA 的疫苗与其他类型的基因治疗在概念上有所不同，因为它们不是设计用于直接杀死癌细胞或使它们对药物的细胞毒性活性敏感，而是引发肿瘤特异性免疫反应。尽管进行了大量的临床前开发，但这种免疫治疗模式在临床实践中的引入仍面临困难。事实上，虽然大多数基于 DNA 的抗癌疫苗被癌症患者很好地耐受，但它们往往无法产生具有治疗意义的临床反应。在本次试验观察中，我们讨论了在癌症治疗中使用基于 DNA 的疫苗的最新进展，讨论了过去 13 个月围绕这一主题产生的文献以及在同一时间框架内启动的临床研究，以评估这种干预的实际治疗潜力。
