趋化因子激动剂在癌细胞上的选择性展示会激活免疫细胞上的甲酰肽受体 1。
Selective Display of a Chemoattractant Agonist on Cancer Cells Activates the Formyl Peptide Receptor 1 on Immune Cells.
机构信息
Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania, 18015, USA.
Department of Chemistry, University of Virginia, Charlottesville, Virginia, 22904, USA.
出版信息
Chembiochem. 2022 Apr 20;23(8):e202100521. doi: 10.1002/cbic.202100521. Epub 2022 Mar 9.
Current immunotherapeutics often work by directing components of the immune system to recognize biomarkers on the surface of cancer cells to generate an immune response. However, variable changes in biomarker distribution and expression can result in inconsistent patient response. The development of a more universal tumor-homing strategy has the potential to improve selectivity and extend therapy to cancers with decreased expression or absence of specific biomarkers. Here, we designed a bifunctional agent that exploits the inherent acidic microenvironment of most solid tumors to selectively graft the surface of cancer cells with a formyl peptide receptor ligand (FPRL). Our approach is based on the pH(Low) insertion peptide (pHLIP), a unique peptide that selectively targets tumors in vivo by anchoring to cancer cells in a pH-dependent manner. We establish that selectively remodeling cancer cells with a pHLIP-based FPRL activates formyl peptide receptors on recruited immune cells, potentially initiating an immune response towards tumors.
目前的免疫疗法通常通过指导免疫系统的成分识别癌细胞表面的生物标志物来产生免疫反应。然而，生物标志物分布和表达的变化会导致患者反应不一致。开发一种更通用的肿瘤归巢策略有可能提高选择性，并将治疗扩展到表达水平降低或缺乏特定生物标志物的癌症。在这里，我们设计了一种双功能试剂，利用大多数实体瘤固有的酸性微环境，选择性地将甲酰肽受体配体（FPRL）接枝到癌细胞表面。我们的方法基于 pH（低）插入肽（pHLIP），这是一种独特的肽，通过以 pH 依赖性方式锚定癌细胞，选择性地在体内靶向肿瘤。我们证实，用基于 pHLIP 的 FPRL 选择性重塑癌细胞会激活募集的免疫细胞上的甲酰肽受体，可能会引发针对肿瘤的免疫反应。
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