Clinica Chirurgica Generale 2, Department of Oncological & Surgical Sciences, University of Padova, via Giustiniani 2, 35128 Padova, Italy.
Curr Med Chem. 2009;16(36):4779-96. doi: 10.2174/092986709789909648.
Anticancer active immunotherapy embodies the ideal antitumor therapy, as it theoretically combines target specificity with long-term disease control. Peptide-based cancer vaccines represent the most specific approach to polarize the immune system against malignant cells, since they are preparations made of single epitopes, the minimal immunogenic region of an antigen. Despite the strong rational, the promising preclinical results and the frequent induction of antigen-specific immune responses, peptide-based cancer vaccines have yielded relatively poor results in the clinical setting, a phenomenon likely due to the immunosuppressive properties of the tumor microenvironment that allow malignant cells to evade both naturally occurring and therapeutically induced immune surveillance. Nevertheless, advances in the engineering of peptides and in our understanding of the molecular mechanisms underlying an effective immune response against tumors have renewed the enthusiasm for peptide-based vaccination regimens in the setting of cancer, and a variety of clinical trials are being conducted based on the use of peptides. This review will describe the most recent insights in the rational design of peptide-based cancer vaccines, as well as the challenges to successful anticancer immunotherapy based on these short amino acid chains.
抗癌主动免疫治疗体现了理想的抗肿瘤治疗,因为它理论上结合了靶向特异性和长期疾病控制。基于肽的癌症疫苗代表了使免疫系统针对恶性细胞产生极化的最特异方法,因为它们是由单个表位(抗原的最小免疫原性区域)制成的制剂。尽管有很强的合理性、有前途的临床前结果和频繁诱导抗原特异性免疫反应,但基于肽的癌症疫苗在临床环境中产生的结果相对较差,这一现象可能是由于肿瘤微环境的免疫抑制特性所致,这些特性使恶性细胞能够逃避自然发生和治疗性诱导的免疫监视。然而,肽的工程学方面的进展以及对针对肿瘤的有效免疫反应的分子机制的理解,为基于肽的疫苗接种方案在癌症中的应用重新注入了热情,并且正在根据使用肽进行各种临床试验。这篇综述将描述基于肽的癌症疫苗的合理设计的最新见解,以及基于这些短氨基酸链的成功抗癌免疫治疗所面临的挑战。