Nanoparticles have attracted considerable interest as cancer vaccine delivery vehicles for inducing sufficient CD8⁺ T cell-mediated immune responses to overcome the low immunogenicity of tumor microenvironments. Our studies described here are the first to examine the effects of clinically-tested human cancer-testis (CT) peptide epitopes within a synthetic nanoparticle. Specifically, we focused on two significant clinical CT targets, the HLA-A2 restricted epitopes of NY-ESO-1 and MAGE-A3, using a viral-mimetic packaging strategy. Our data shows that simultaneous delivery of a NY-ESO-1 epitope (SLLMWITQV) and CpG using the E2 subunit assembly of pyruvate dehydrogenase (E2 nanoparticle), resulted in a 25-fold increase in specific IFN-γ secretion in HLA-A2 transgenic mice. This translated to a 15-fold increase in lytic activity toward target cancer cells expressing the antigen. Immunization with a MAGE-A3 epitope (FLWGPRALV) delivered with CpG in E2 nanoparticles yielded an increase in specific IFN-γ secretion and cell lysis by 6-fold and 9-fold, respectively. Furthermore, combined delivery of NY-ESO-1 and MAGE-A3 antigens in E2 nanoparticles yielded an additive effect that increased lytic activity towards cells bearing NY-ESO-1⁺ and MAGE-A3⁺. Our investigations demonstrate that formulation of CT antigens within a nanoparticle can significantly enhance antigen-specific cell-mediated responses, and the combination of the two antigens in a vaccine can preserve the increased individual responses that are observed for each antigen alone.

作为诱导足够CD8 ^+的癌症疫苗输送工具，纳米粒子已引起人们极大的兴趣。T细胞介导的免疫反应可克服肿瘤微环境的低免疫原性。这里描述的我们的研究是第一个检查合成纳米粒子中经过临床测试的人类癌症-睾丸（CT）肽表位的作用的研究。具体来说，我们采用病毒模拟包装策略，重点研究了两个重要的临床CT靶点，即HLA-A2限制性NY-ESO-1和MAGE-A3抗原决定簇。我们的数据表明，使用丙酮酸脱氢酶（E2纳米颗粒）的E2亚基组装体同时递送NY-ESO-1表位（SLLMWITQV）和CpG，导致转基因HLA-A2中特异性IFN-γ分泌增加了25倍老鼠。这转化为针对表达抗原的靶癌细胞的裂解活性增加了15倍。用Ep纳米颗粒中的CpG递送的MAGE-A3表位（FLWGPRALV）进行的免疫作用分别使特异性IFN-γ分泌和细胞裂解增加了6倍和9倍。此外，E2纳米颗粒中NY-ESO-1和MAGE-A3抗原的联合递送产生累加效应，增加了对带有NY-ESO-1的细胞的裂解活性⁺和MAGE-A3 ⁺。我们的研究表明，在纳米粒子中配制CT抗原可以显着增强抗原特异性细胞介导的反应，并且疫苗中两种抗原的组合可以保留单独针对每种抗原观察到的增加的个体反应。