Jendryczko Karolina, Chudzian Julia, Skinder Natalia, Opaliński Łukasz, Rzeszótko Jakub, Wiedlocha Antoni, Otlewski Jacek, Szlachcic Anna
Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, 50383 Wroclaw, Poland.
Department of Molecular Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, 0379 Oslo, Norway.
Cancers (Basel). 2020 Oct 15;12(10):2992. doi: 10.3390/cancers12102992.
Fibroblast growth factor receptors (FGFRs) are emerging targets for directed cancer therapy. Presented here is a new FGFR1-targeting conjugate, the peptibodyF2, which employs peptibody, a fusion of peptide and the Fc fragment of human IgG as a selective targeting agent and drug carrier. Short peptide based on FGF2 sequence was used to construct a FGFR1-targeting peptibody. We have shown that this peptide ensures specific delivery of peptibodyF2 into FGFR1-expressing cells. In order to use peptibodyF2 as a delivery vehicle for cytotoxic drugs, we have conjugated it with MMAE, a drug widely used in antibody-drug conjugates for targeted therapy. Resulting conjugate shows high and specific cytotoxicity towards FGFR1-positive cells, i.e., squamous cell lung carcinoma NCI-H520, while remaining non-toxic for FGFR1-negative cells. Such peptibody-drug conjugate can serve as a basis for development of therapy for tumors with overexpressed or malfunctioning FGFRs.
成纤维细胞生长因子受体（FGFRs）正成为定向癌症治疗的新兴靶点。本文介绍了一种新的靶向FGFR1的偶联物——肽抗体F2，它采用肽抗体（一种肽与人类IgG的Fc片段的融合物）作为选择性靶向剂和药物载体。基于FGF2序列的短肽被用于构建靶向FGFR1的肽抗体。我们已经证明，这种肽可确保肽抗体F2特异性递送至表达FGFR1的细胞中。为了将肽抗体F2用作细胞毒性药物的递送载体，我们将其与MMAE（一种广泛用于抗体-药物偶联物靶向治疗的药物）偶联。所得偶联物对FGFR1阳性细胞，即肺鳞状细胞癌NCI-H520，显示出高特异性细胞毒性，而对FGFR1阴性细胞仍无毒。这种肽抗体-药物偶联物可作为开发针对FGFRs过表达或功能异常肿瘤的治疗方法的基础。
