Laboratory of Nano- and Translational Medicine, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Nat Nanotechnol. 2017 Sep;12(9):877-882. doi: 10.1038/nnano.2017.113. Epub 2017 Jun 26.
Immunotherapy holds tremendous promise for improving cancer treatment. To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the 'abscopal effect'. Unfortunately, response rates for this strategy remain low. Herein we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NP formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent on the NP surface properties. We showed that AC-NPs deliver tumour-specific proteins to antigen-presenting cells (APCs) and significantly improve the efficacy of αPD-1 (anti-programmed cell death 1) treatment using the B16F10 melanoma model, generating up to a 20% cure rate compared with 0% without AC-NPs. Mechanistic studies revealed that AC-NPs induced an expansion of CD8 cytotoxic T cells and increased both CD4T/T and CD8T/T ratios (T, regulatory T cells). Our work presents a novel strategy to improve cancer immunotherapy with nanotechnology.
免疫疗法在改善癌症治疗方面具有巨大的潜力。将放射疗法与免疫疗法联合使用已被证明可以改善免疫反应，并引发“远隔效应”。不幸的是，这种策略的反应率仍然很低。在此，我们报告了一种利用抗原捕获纳米颗粒（AC-NP）的改良癌症免疫治疗方法。我们设计了几种 AC-NP 制剂，并证明了每种 AC-NP 制剂捕获的蛋白质抗原集取决于 NP 的表面特性。我们表明，AC-NP 将肿瘤特异性蛋白递送至抗原呈递细胞（APC），并显著提高了 αPD-1（抗程序性细胞死亡 1）治疗 B16F10 黑色素瘤模型的疗效，与不使用 AC-NP 相比，治愈率高达 20%，而治愈率为 0%。机制研究表明，AC-NP 诱导了 CD8 细胞毒性 T 细胞的扩增，并增加了 CD4T/T 和 CD8T/T 比值（T，调节性 T 细胞）。我们的工作提出了一种利用纳米技术改善癌症免疫疗法的新策略。
