Cancer Immunology & Immunotherapy Center, Saint Savas Cancer Hospital, Athens, Greece.
Immunotherapy. 2013 May;5(5):497-511. doi: 10.2217/imt.13.24.
Toll-like receptor (TLR) agonists possess remarkable properties, particularly with regard to dendritic cell activation, promoting Th1-type cytokine production and optimizing cytotoxic T-cell responses. Preclinical and clinical studies conducted to date show that TLR agonists can improve currently applied anticancer vaccination protocols. Although these have resulted in the US FDA approval of three TLR agonists for use in humans, their abundant application encounters limitations, principally due to dose-limiting toxicity evoking from systemic cytokine production. Here, using selected examples of clinical studies, we provide a concise review regarding the knowledge acquired thus far on the adjuvant use of TLR agonists as cancer vaccine components. We also provide evidence on the exploitation of a novel TLR agonist, prothymosin-α, which enhances the efficacy of tumor-reactive effectors without causing severe adverse effects.
toll 样受体（TLR）激动剂具有显著的特性，特别是在树突状细胞激活、促进 Th1 型细胞因子产生和优化细胞毒性 T 细胞反应方面。迄今为止进行的临床前和临床研究表明，TLR 激动剂可以改善目前应用的抗癌疫苗方案。尽管这些研究已经导致美国 FDA 批准了三种 TLR 激动剂用于人体，但它们的广泛应用受到限制，主要是由于全身细胞因子产生引起的剂量限制毒性。在这里，我们通过选择临床研究的例子，对迄今为止关于 TLR 激动剂作为癌症疫苗成分的佐剂应用的知识进行了简明的回顾。我们还提供了利用新型 TLR 激动剂胸腺肽-α的证据，该激动剂增强了肿瘤反应效应物的疗效，而不会引起严重的不良反应。
