Faculty of Pharmacy, FFUC, University of Coimbra, 3000-548, Coimbra, Portugal; Center for Neuroscience and Cell Biology, CNC, University of Coimbra, 3004-504, Coimbra, Portugal.
Center for Neuroscience and Cell Biology, CNC, University of Coimbra, 3004-504, Coimbra, Portugal; Tecnimede Group, 2710-089, Sintra, Portugal.
Pharmacol Res. 2021 Feb;164:105309. doi: 10.1016/j.phrs.2020.105309. Epub 2020 Nov 16.
In the last decade, immunotherapy led to a paradigm shift in the treatment of numerous malignancies. Alongside with monoclonal antibodies blocking programmed cell death receptor-1 (PD-1)/PD-L1 and cytotoxic T- lymphocyte antigen 4 (CTLA-4) immune checkpoints, cell-based approaches such as CAR-T cells and dendritic cell (DC) vaccines have strongly contributed to pushing forward this thrilling field. While initial strategies were mainly focused on monotherapeutic regimens, it is now consensual that the combination of immunotherapies tackling multiple cancer hallmarks can result in superior clinical outcomes. Here, we review in depth the pharmacological combination of DC-based vaccines that boost tumour elimination by eliciting and expanding effector immune cells, with the PD-1 inhibitor Nivolumab that allows blocking key tumour immune escape mechanisms. This combination represents an important step in cancer therapy, with a significant enhancement in patient survival in several types of tumours, paving an important way in establishing combinatorial immunotherapeutic strategies as first-line treatments.
在过去的十年中,免疫疗法在治疗众多恶性肿瘤方面带来了范式转变。除了阻断程序性细胞死亡受体-1(PD-1)/PD-L1 和细胞毒性 T 淋巴细胞相关抗原 4(CTLA-4)免疫检查点的单克隆抗体外,基于细胞的方法,如嵌合抗原受体 T 细胞(CAR-T 细胞)和树突状细胞(DC)疫苗,也为推动这一激动人心的领域做出了巨大贡献。虽然最初的策略主要集中在单药治疗方案上,但现在人们已经达成共识,即联合针对多种癌症特征的免疫疗法可以带来更好的临床结果。在这里,我们深入探讨了基于 DC 的疫苗与 PD-1 抑制剂纳武利尤单抗的药理学组合,该组合通过引发和扩增效应免疫细胞来增强肿瘤消除作用,纳武利尤单抗可阻断关键的肿瘤免疫逃逸机制。这种组合是癌症治疗的重要一步,在多种类型的肿瘤中显著提高了患者的生存率,为将组合免疫治疗策略作为一线治疗奠定了重要基础。