Cancer Immunology and Immunotherapy Center, St. Savas Cancer Hospital, Athens, Greece.
Cancer. 2010 May 1;116(9):2071-80. doi: 10.1002/cncr.24988.
The use of synthetic peptides as vaccines aimed at the induction of therapeutic CD8-positive T-cell responses against tumor cells initially experienced great enthusiasm, mostly because of advances in vaccine technology, including design, synthesis, and delivery. However, despite impressive results in animal models, the application of such vaccines in humans has met with only limited success. The therapeutic activity of vaccine-stimulated, tumor-specific, CD8-positive T cells can be hampered through the physical burden of the tumor, tolerance mechanisms, and local factors within the tumor microenvironment. Recently, accumulating evidence has suggested that combining a peptide-based therapeutic vaccination with conventional chemotherapy can uncover the full potential of the antitumor immune response, increasing the success of immunotherapy. In addition, therapeutic vaccination in the preventive setting has been extremely effective in eliciting antitumor responses in preclinical tumor models and has demonstrated good promise clinically in patients with minimal residual disease. The rationale behind preventive vaccination is that patients with minimal tumor burden still have a fully competent immune system capable of developing robust antitumor responses. Finally, therapeutic CD8-positive T-cell peptide vaccines have been improved by coimmunization with T-helper epitopes expressed on long peptides.
最初，人们对合成肽疫苗寄予厚望，希望其能诱导针对肿瘤细胞的治疗性 CD8 阳性 T 细胞反应，这主要是因为疫苗技术取得了进展，包括设计、合成和递送方面。然而，尽管在动物模型中取得了令人印象深刻的结果，但此类疫苗在人类中的应用仅取得了有限的成功。疫苗刺激的、肿瘤特异性的 CD8 阳性 T 细胞的治疗活性可能会受到肿瘤的物理负担、耐受机制以及肿瘤微环境中的局部因素的阻碍。最近，越来越多的证据表明，将基于肽的治疗性疫苗接种与常规化疗相结合，可以挖掘抗肿瘤免疫反应的全部潜力，从而提高免疫疗法的成功率。此外，预防性疫苗接种在临床前肿瘤模型中非常有效地引发了抗肿瘤反应，并在有微小残留病的患者中显示出良好的临床前景。预防性疫苗接种的基本原理是，肿瘤负担较小的患者仍具有完全健全的免疫系统，能够产生强大的抗肿瘤反应。最后，通过与长肽上表达的 T 辅助表位共同免疫，治疗性 CD8 阳性 T 细胞肽疫苗得到了改进。
