Neoantigen cancer vaccines hold great promise for cancer treatment but are often limited by the immunosuppressive tumor environment. Now, as described in Nature, Redenti et al. have overcome this issue by harnessing the natural capacity of bacteria to colonize tumors and trigger immune responses. They have developed a microbial system that produces and delivers distinct sets of neoantigens to elicit potent killing of solid tumors.

Redenti et al. engineered the probiotic Escherichia coli Nissle 1917, introducing several modifications that enhance therapeutic use. First, the authors removed E. coli cryptic plasmids and deleted the Lon and OmpT proteases, which enhanced the production of synthetic neoantigen constructs by 80-fold. This engineered vector was four times more susceptible to phagocytosis than the wild type, increasing uptake by antigen-presenting cells. Next, the authors co-expressed listeriolysin O, a Listeria-derived pore-forming protein that permeabilizes the phagolysosomal membrane, to induce cytosolic delivery of neoantigens for enhanced presentation to CD8⁺ T cells and to promote T helper 1 cell immunity.

新抗原癌症疫苗在癌症治疗方面前景广阔，但往往受到免疫抑制性肿瘤环境的限制。现在，正如 Nature 上所描述的，Redenti 等人通过利用细菌的天然能力定植肿瘤并触发免疫反应来克服了这个问题。他们开发了一种微生物系统，可以产生和递送不同的新抗原集，以引发对实体瘤的有效杀伤。

Redenti 等人于 1917 年设计了益生菌大肠杆菌 Nissle，引入了几种增强治疗用途的修饰。首先，作者去除了大肠杆菌隐蔽质粒并删除了 Lon 和 OmpT 蛋白酶，从而将合成新抗原构建体的产生提高了 80 倍。这种工程载体对吞噬作用的敏感性是野生型的 4 倍，增加了抗原呈递细胞的摄取。接下来，作者共表达李斯特菌溶血素 O，这是一种李斯特菌衍生的成孔蛋白，可透化吞噬溶酶体膜，以诱导新抗原的胞质递送，以增强对 CD8⁺ T 细胞的呈递并促进 T 辅助性 1 细胞免疫。