Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon, 34141, Republic of Korea.
Center for Precision Bio-Nanomedicine, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon, 34141, Republic of Korea.
Angew Chem Int Ed Engl. 2020 Aug 17;59(34):14628-14638. doi: 10.1002/anie.202006117. Epub 2020 Jul 6.
We describe a small lipid nanoparticle (SLNP)-based nanovaccine platform and a new combination treatment regimen. Tumor antigen-displaying, CpG adjuvant-embedded SLNPs (OVA -SLNP@CpG) were prepared from biocompatible phospholipids and a cationic cholesterol derivative. The resulting nanovaccine showed highly potent antitumor efficacy in both prophylactic and therapeutic E.G7 tumor models. However, this vaccine induced T cell exhaustion by elevating PD-L1 expression, leading to tumor recurrence. Thus, the nanovaccine was combined with simultaneous anti-PD-1 antibody treatment, but the therapeutic efficacy of this regimen was comparable to that of the nanovaccine alone. Finally, mice that showed a good therapeutic response after the first cycle of immunization with the nanovaccine underwent a second cycle together with anti-PD-1 therapy, resulting in suppression of tumor relapse. This suggests that the antitumor efficacy of combinations of nanovaccines with immune checkpoint blockade therapy is dependent on treatment sequence and the timing of each modality.
我们描述了一种基于小脂质纳米颗粒（SLNP）的纳米疫苗平台和一种新的联合治疗方案。肿瘤抗原展示、CpG 佐剂嵌入的 SLNP（OVA-SLNP@CpG）由生物相容性磷脂和阳离子胆固醇衍生物制备而成。这种新型纳米疫苗在预防性和治疗性 E.G7 肿瘤模型中均显示出高效的抗肿瘤疗效。然而，该疫苗通过上调 PD-L1 表达诱导 T 细胞耗竭，导致肿瘤复发。因此，纳米疫苗与同时使用抗 PD-1 抗体治疗相结合，但该方案的治疗效果与纳米疫苗单独使用相当。最后，在第一轮免疫接种纳米疫苗后表现出良好治疗反应的小鼠与抗 PD-1 治疗一起进行第二轮治疗，从而抑制了肿瘤复发。这表明纳米疫苗与免疫检查点阻断治疗联合的抗肿瘤疗效取决于治疗顺序和每种治疗方式的时机。
