Abstract：
Personalized cancer vaccines targeting specific neoantigens have been envisioned as one of the most promising approaches in cancer immunotherapy. However, the physicochemical variability of the identified neoantigens limits their efficacy as well as vaccine manufacturing in a uniform format. Herein, we developed a uniform nanovaccine platform based on poly(2-oxazoline)s (POx) to chemically conjugate neoantigen peptides, regardless of their physicochemical properties. This vaccine system could self-assemble into nanoparticles with uniform size (around 50 nm) and improve antigen accumulation as well as infiltration in the lymph node to increase antigen presentation. In vivo vaccination using this system conjugated with three predicted peptide neoantigen peptides from the MC38 tumor cell line induced 100% robust CD8+ T cell responses and superior tumor clearance compared to free peptides. This POx-based vaccine carrier represents a generalizable approach to increase the availability and efficacy of screened neoantigen peptides for a personalized cancer vaccine.
摘要：
靶向特异性新抗原的个性化癌症疫苗已被设想为癌症免疫疗法中最有希望的方法之一。然而,鉴定的新抗原的物理化学变异性限制了它们的功效以及统一格式的疫苗生产.在这里，我们开发了一种基于聚（2-恶唑啉）（POx）的统一纳米疫苗平台，以化学缀合新抗原肽，不管它们的物理化学性质。该疫苗系统可以自组装成具有均匀尺寸(约50nm)的纳米颗粒,并改善抗原积累以及淋巴结中的浸润以增加抗原呈递。与游离肽相比,使用与来自MC38肿瘤细胞系的三种预测的肽新抗原肽缀合的该系统的体内疫苗接种诱导100%稳健的CD8+T细胞应答和优异的肿瘤清除。这种基于POx的疫苗载体代表了提高个性化癌症疫苗的筛选的新抗原肽的可用性和功效的可推广方法。
