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Poxviral vectors for cancer immunotherapy.

机译：用于癌症免疫治疗的痘病毒载体。

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INTRODUCTION: Poxviral vaccines have been given to over 1 billion people in the successful global eradication of smallpox. Recombinant poxviruses have been investigated extensively as a novel immunotherapy for cancer, undergoing several iterations to optimize their immunogenicity and efficacy. The current platform expressing multiple costimulatory molecules plus a tumor-associated antigen such as PSA, that is, PSA-TRICOM (PROSTVAC-V/F), is promising and is currently in a Phase III randomized, placebo-controlled clinical trial in metastatic castration-resistant prostate cancer. AREAS COVERED: This review discusses the clinical development of poxviral-based cancer vaccines, with a particular focus on the rationale for combining vaccines with other treatment modalities, including radiotherapy, chemotherapy, hormonal therapy, other immune-based therapies and molecularly targeted therapy. We also discuss the importance of appropriate patient selection in clinical trial design. EXPERT OPINION: Preclinical and early clinical studies employing poxviral-vector vaccines have shown promising results with this novel immunologic approach, both alone and combined with other therapies. The challenges of translating the science of immunotherapy to clinical practice include clinical trial design that includes appropriate patient selection, appropriate end points and identification of meaningful surrogate biomarkers.
机译：简介：在全球成功根除天花的过程中，已向超过10亿人接种了痘病毒疫苗。重组痘病毒已作为一种新型的癌症免疫疗法进行了广泛研究，经过多次迭代以优化其免疫原性和功效。目前表达多种共刺激分子以及肿瘤相关抗原（例如PSA）的平台，即PSA-TRICOM（PROSTVAC-V / F），前景广阔，目前正在进行转移cast割的III期随机，安慰剂对照临床试验耐药性前列腺癌。涵盖的领域：这篇综述讨论了基于痘病毒的癌症疫苗的临床开发，特别侧重于将疫苗与其他治疗方式（包括放疗，化学疗法，激素疗法，其他基于免疫的疗法和分子靶向疗法）相结合的原理。我们还将讨论在临床试验设计中适当选择患者的重要性。专家意见：使用痘病毒载体疫苗的临床前和早期临床研究表明，采用这种新颖的免疫学方法，无论是单独使用还是与其他疗法联合使用，都有望获得令人满意的结果。将免疫治疗科学转化为临床实践所面临的挑战包括临床试验设计，其中包括适当的患者选择，适当的终点以及有意义的替代生物标志物的鉴定。

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