Wang Jingjing, Sun Bing, Sun Luyao, Niu Xueming, Li Li, Xu Zhi Ping
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.
Biomater Sci. 2023 Mar 14;11(6):2020-2032. doi: 10.1039/d2bm01432g.
Cancer cell membranes (CCMs) have emerged as advanced cancer treatment vaccines to boost the immune response against cancer and have shown great potential in cancer immunotherapy. However, the CCM vaccine confronts the challenges of a weak and short immune response, ascribed to the immune escape and low accumulation of the CCM in antigen presentation cells (APCs). To overcome these shortcomings, we devised a "Trojan horse" CCM nano-vaccine delivered by layered double hydroxide (LDH) nanoparticles with mannose targeting and bovine serum albumin (BSA) coating to overcome the immune escape challenge, efficiently boosting the immune response to cancer cells. This "Trojan horse" CCM nano-vaccine, named LGCMB, is constructed by assembling the CCM antigen on CpG-LDH (LG), followed by mannose-BSA coating for the APC target and BSA coating to mask immune-escape protein on the CCM. The cellular uptake and maturation data have clearly shown that the BSA coating strategy with mannose as a "Trojan horse" efficiently targeted APCs (macrophages and DCs) and effectively inhibited the immune escape of the CCM, competently stimulating the APC maturation. Moreover, LGCMB can migrate to the draining lymph nodes (LNs) and trigger tumor-specific CD8 T cell responses . As expected, the LGCMB nano-vaccine significantly suppressed tumor growth , showing great potential as a precision cancer vaccine.
癌细胞膜（CCMs）已成为先进的癌症治疗疫苗，用于增强针对癌症的免疫反应，并在癌症免疫治疗中显示出巨大潜力。然而，CCM疫苗面临免疫反应微弱且短暂的挑战，这归因于CCM在抗原呈递细胞（APC）中的免疫逃逸和低积累。为了克服这些缺点，我们设计了一种“特洛伊木马”CCM纳米疫苗，由具有甘露糖靶向性和牛血清白蛋白（BSA）涂层的层状双氢氧化物（LDH）纳米颗粒递送，以克服免疫逃逸挑战，有效增强对癌细胞的免疫反应。这种“特洛伊木马”CCM纳米疫苗名为LGCMB，通过在CpG-LDH（LG）上组装CCM抗原构建，随后进行甘露糖-BSA涂层以靶向APC，以及BSA涂层以掩盖CCM上的免疫逃逸蛋白。细胞摄取和成熟数据清楚地表明，以甘露糖作为“特洛伊木马”的BSA涂层策略有效地靶向了APC（巨噬细胞和树突状细胞），并有效抑制了CCM的免疫逃逸，有力地刺激了APC成熟。此外，LGCMB可以迁移至引流淋巴结（LNs）并触发肿瘤特异性CD8 T细胞反应。正如预期的那样，LGCMB纳米疫苗显著抑制了肿瘤生长，显示出作为精准癌症疫苗的巨大潜力。
