Key Laboratory for Translational Medicine, The First Affiliated Hospital of Huzhou University School of Medicine, Huzhou, 313000, Zhejiang, China.
Department of Clinical Medicine, Huzhou University School of Medicine, Huzhou, 313000, Zhejiang, China.
Drug Deliv Transl Res. 2019 Dec;9(6):1095-1105. doi: 10.1007/s13346-019-00652-z.
Poly(lactic-co-glycolic) acid (PLGA) has been successfully used in drug delivery and biomaterial applications, but very little attention has been directed towards the potential in vivo effects of peptide-loaded PLGA nanoparticles (NPs), specifically the potency of intravenous (IV) STEAP peptide-loaded PLGA-NP (nanovaccine) dosing and whether STEAP-specific CD8 T cells directly play a key role in tumor inhibition. To address these concerns, syngeneic prostate cancer mouse models were established and treated with either mSTEAP peptide emulsified in incomplete Freund's adjuvant (IFA) via subcutaneous (SC) injection or mSTEAP peptide nanovaccine containing the same amount of peptide via IV or SC injection. Meanwhile, mice were treated with either CD8b mAb followed by nanovaccine treatment, free mSTEAP peptide, or empty PLGA-NPs. Immune responses in these mice were examined using cytotoxicity assays at 14 days after treatment. Tumor size and survival in various treatment groups were measured and monitored. The results demonstrated that mSTEAP peptide nanovaccine resulted in tumor inhibition by eliciting a significantly stronger CD8 T cell immune response when compared with the controls. Moreover, the survival periods of mice treated with mSTEAP nanovaccine were significantly longer than those of mice treated with mSTEAP peptide emulsified in IFA or the treatment controls. Additionally, it was observed that the peptide nanovaccine was mainly distributed in the mouse liver and lungs after IV injection. These findings suggest that the peptide nanovaccine is a promising immunotherapeutic approach and offers a new opportunity for prostate cancer therapies.
聚（乳酸-共-乙醇酸）（PLGA）已成功用于药物输送和生物材料应用，但很少有人关注载肽 PLGA 纳米颗粒（NPs）的体内潜在影响，特别是静脉内（IV）STEAP 肽载 PLGA-NP（纳米疫苗）给药的效力，以及 STEAP 特异性 CD8 T 细胞是否直接在肿瘤抑制中发挥关键作用。为了解决这些问题，建立了同种前列腺癌小鼠模型，并通过皮下（SC）注射用 mSTEAP 肽乳化的不完全弗氏佐剂（IFA）或含有相同量肽的 mSTEAP 肽纳米疫苗通过 IV 或 SC 注射进行治疗。同时，用 CD8b mAb 处理后用纳米疫苗处理、游离 mSTEAP 肽或空 PLGA-NPs 处理小鼠。在治疗后 14 天使用细胞毒性测定法检查这些小鼠中的免疫反应。测量和监测各种治疗组中的肿瘤大小和存活。结果表明，与对照组相比，mSTEAP 肽纳米疫苗通过引发更强的 CD8 T 细胞免疫反应导致肿瘤抑制。此外，用 mSTEAP 纳米疫苗治疗的小鼠的存活期明显长于用 IFA 乳化的 mSTEAP 肽或治疗对照治疗的小鼠。此外，观察到肽纳米疫苗在 IV 注射后主要分布在小鼠的肝脏和肺部。这些发现表明，肽纳米疫苗是一种有前途的免疫治疗方法，为前列腺癌治疗提供了新的机会。
