Harrop Richard, John Justin, Carroll Miles W
Oxford BioMedica (U.K.) Ltd., Oxford Science Park, Oxford, OX4 4GA U.K.
Adv Drug Deliv Rev. 2006 Oct 1;58(8):931-47. doi: 10.1016/j.addr.2006.05.005. Epub 2006 Aug 16.
To date cancer vaccines have yet to show efficacy in a phase III trial. However, the clinical benefit seen with monoclonal antibody mediated therapies (e.g., Herceptin) has provided proof of principle that immune responses directed against tumour-associated antigens could have therapeutic potential. The failure of past cancer vaccine trials is likely due to several factors including the inappropriate choice of tumour antigen, use of an unoptimised antigen delivery system or vaccination schedule or selection of the wrong patient group. Any one of these variables could potentially result in the induction of an immune response of insufficient magnitude to deliver clinical benefit. Live recombinant viral vaccines have been used in the development of cancer immunotherapy approaches for the past 10 years. Though such vectors are self-adjuvanted and offer the ability to express multiple tumour-associated antigens (TAAs) along with an array of immune co-factors, arguably, they have yet to demonstrate convincing efficacy in pivotal clinical trials. However, in recent years, more coordinated studies have revealed mechanisms to optimise current vectors and have lead to the development of new advantageous vector systems. In this review, we highlight that live recombinant viral vectors provide a versatile and effective antigen delivery system and describe the optimal properties of an effective viral vector. Additionally, we discuss the advantages and disadvantages of the panel of recombinant viral systems currently available to cancer vaccinologists and how they can work in synergy in heterologous prime boost protocols and with other treatment modalities.
迄今为止,癌症疫苗在III期试验中尚未显示出疗效。然而,单克隆抗体介导的疗法(如赫赛汀)所展现的临床益处为针对肿瘤相关抗原的免疫反应具有治疗潜力这一原理提供了证据。过去癌症疫苗试验的失败可能归因于多个因素,包括肿瘤抗原选择不当、使用未优化的抗原递送系统或疫苗接种方案,或者选错了患者群体。这些变量中的任何一个都可能导致诱导出强度不足以带来临床益处的免疫反应。在过去10年里,活重组病毒疫苗已被用于癌症免疫治疗方法的研发。尽管这类载体具有自身佐剂作用,并且能够表达多种肿瘤相关抗原(TAAs)以及一系列免疫辅助因子,但可以说,它们在关键临床试验中尚未展现出令人信服的疗效。然而,近年来,更多协同研究揭示了优化现有载体的机制,并促成了新的优势载体系统的开发。在本综述中,我们强调活重组病毒载体提供了一种通用且有效的抗原递送系统,并描述了有效病毒载体的最佳特性。此外,我们讨论了目前癌症疫苗学家可用的一系列重组病毒系统的优缺点,以及它们如何在异源初免 - 加强方案中以及与其他治疗方式协同发挥作用。