A growing class of immunotherapeutics work by redirecting components of the immune system to recognize markers on the surface of cancer cells. However, such modalities will remain confined to a relatively small subgroup of patients because of the lack of universal targetable tumor biomarkers among all patients. Here, we designed a unique class of agents that exploit the inherent acidity of solid tumors to selectively graft cancer cells with immuno-engager epitopes. Our targeting approach is based on pHLIP, a unique peptide that selectively targets tumors in vivo by anchoring to cancer cell surfaces in a pH-dependent manner. We established that pHLIP-antigen conjugates trigger the recruitment of antibodies to the surface of cancer cells and induce cytotoxicity by peripheral blood mononuclear and engineered NK cells. These results indicate that these agents have the potential to be applicable to treating a wide range of solid tumors and to circumvent problems associated with narrow windows of selectivity.

中文翻译：

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抗原表位对癌细胞的pH依赖性接枝促进了选择性抗体介导的细胞毒性。

越来越多的免疫治疗药通过重定向免疫系统的成分来识别癌细胞表面的标志物而起作用。然而，由于所有患者中缺乏通用的可靶向肿瘤生物标记物，因此这种方式将仍然局限于相对较小的患者亚组。在这里，我们设计了独特的一类药物，这些药物利用实体瘤固有的酸性来选择性地将癌细胞与免疫结合抗原决定簇移植。我们的靶向方法基于pHLIP，pHLIP是一种独特的肽，通过以pH依赖的方式锚定在癌细胞表面上选择性地在体内靶向肿瘤。我们确定，pHLIP-抗原结合物可触发抗体募集至癌细胞表面，并通过外周血单核和工程NK细胞诱导细胞毒性。