Frega Giorgio, Wu Qi, Le Naour Julie, Vacchelli Erika, Galluzzi Lorenzo, Kroemer Guido, Kepp Oliver
Equipe labellisée par la Ligue Contre le Cancer, Université de Paris, Sorbonne Université, INSERM UMR1138, Centre de Recherche des Cordeliers, Paris, France.
Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France.
Oncoimmunology. 2020 Jul 21;9(1):1796002. doi: 10.1080/2162402X.2020.1796002.
Resiquimod (R848) and motolimod (VTX-2337) are second-generation experimental derivatives of imiquimod, an imidazoquinoline with immunostimulatory properties originally approved by the US Food and Drug Administration for the topical treatment of actinic keratosis and genital warts more than 20 years ago. Both resiquimod and motolimod operate as agonists of Toll-like receptor 7 (TLR7) and/or TLR8, in thus far delivering adjuvant-like signals to antigen-presenting cells (APCs). In line with such an activity, these compounds are currently investigated as immunostimulatory agents for the treatment of various malignancies, especially in combination with peptide-based, dendritic cell-based, cancer cell lysate-based, or DNA-based vaccines. Here, we summarize preclinical and clinical evidence recently collected to support the development of resiquimod and motolimod and other TLR7/TLR8 agonists as anticancer agents.
瑞喹莫德（R848）和莫托莫德（VTX - 2337）是咪喹莫特的第二代实验性衍生物，咪喹莫特是一种咪唑喹啉，具有免疫刺激特性，20多年前最初被美国食品药品监督管理局批准用于光化性角化病和尖锐湿疣的局部治疗。瑞喹莫德和莫托莫德均作为Toll样受体7（TLR7）和/或TLR8的激动剂发挥作用，从而向抗原呈递细胞（APC）传递类似佐剂的信号。鉴于这种活性，目前正在研究这些化合物作为免疫刺激剂用于治疗各种恶性肿瘤，特别是与基于肽、基于树突状细胞、基于癌细胞裂解物或基于DNA的疫苗联合使用时。在此，我们总结了最近收集的临床前和临床证据，以支持瑞喹莫德、莫托莫德及其他TLR7/TLR8激动剂作为抗癌药物的开发。
