State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing 100190, China.
Biomaterials. 2018 Aug;174:54-66. doi: 10.1016/j.biomaterials.2018.05.015. Epub 2018 May 10.
Cancer immunotherapy has shown tremendous progresses in recent years for various cancers and layered double hydroxide (LDH) nanoparticles are demonstrated as effective adjuvants for protein-based vaccines. This research further shows that the colloidal stability of LDH-based vaccines significantly influences the therapeutic efficacy and LDH nanoparticles are able to adjuvant multiple tumor-associated antigen peptides to provoke strong cell-mediated immune responses for effective inhibition of cancer growth. The LDH-based multi-target therapeutic vaccines were constructed by assembling epitope peptides and CpG onto LDH nanoparticles. Using melanoma as the model cancer and Tyrosinase-related protein 2 (Trp2) peptide as the model antigen, we demonstrated that dispersion-stable LDH-based vaccine induced stronger cytotoxic T-lymphocyte (CTL) responses and significantly inhibited tumor growth in comparison with aggregated LDH-based vaccine. We further constructed multi-target dispersion-stable LDH-based vaccine by co-loading Trp2, two mutated epitopes (M27 and M30) and CpG, which showed remarkable inhibition of melanoma growth. These results suggest that dispersion-stable LDH nanoparticles are an ideal platform to load multi-antigens and immune stimulants as effective personalized therapeutic cancer vaccines.
近年来，癌症免疫疗法在各种癌症方面取得了巨大进展，层状双氢氧化物（LDH）纳米粒子被证明是蛋白质疫苗的有效佐剂。本研究进一步表明，基于 LDH 的疫苗的胶体稳定性显著影响治疗效果，LDH 纳米粒子能够辅助多种肿瘤相关抗原肽，引发强烈的细胞免疫反应，有效抑制癌症生长。基于 LDH 的多靶治疗疫苗通过将表位肽和 CpG 组装到 LDH 纳米粒子上构建。本研究以黑色素瘤为模型癌症，酪氨酸酶相关蛋白 2（Trp2）肽为模型抗原，结果表明，与聚集的 LDH 基疫苗相比，分散稳定的 LDH 基疫苗诱导更强的细胞毒性 T 淋巴细胞（CTL）反应，并显著抑制肿瘤生长。我们进一步构建了共加载 Trp2、两个突变表位（M27 和 M30）和 CpG 的多靶分散稳定的 LDH 基疫苗，显著抑制了黑色素瘤的生长。这些结果表明，分散稳定的 LDH 纳米粒子是作为有效的个性化治疗癌症疫苗负载多种抗原和免疫刺激剂的理想平台。
