Weigel Kelsey J, Shen Luqun, Thomas Clayton L, Alber Daniel, Drapalik Lauren, Schafer Zachary T, Lee Shaun W
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA.
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA ; Eck Institute for Global Health, University of Notre Dame, Notre Dame, Indiana, USA.
FEBS Open Bio. 2015 Mar 14;5:202-8. doi: 10.1016/j.fob.2015.03.005. eCollection 2015.
Immunotoxins are chimeric proteins comprising a specific cellular targeting domain linked to a cytotoxic factor. Here we describe the design and use of a novel, peptide-based immunotoxin that can initiate selective cytotoxicity on ErbB2-positive cells. ErbB2 is a receptor tyrosine kinase that is overexpressed in the tumor cells of approximately 30% of breast cancer patients. Immunotoxin candidates were designed to incorporate a targeting ligand with affinity for ErbB2 along with a membrane lysin-based toxin domain. One particular peptide candidate, NL1.1-PSA, demonstrated selective cytotoxicity towards ErbB2-overexpressing cell lines. We utilized a bioengineering strategy to show that recombinant NL1.1-PSA immunotoxin expression by Escherichia coli also conferred selective cytotoxicity towards ErbB2-overexpressing cells. Our findings hold significant promise for the use of effective immunotoxins in cancer therapeutics.
免疫毒素是一种嵌合蛋白，由与细胞毒性因子相连的特定细胞靶向结构域组成。在此，我们描述了一种新型的基于肽的免疫毒素的设计与应用，该免疫毒素可对ErbB2阳性细胞引发选择性细胞毒性。ErbB2是一种受体酪氨酸激酶，在约30%的乳腺癌患者的肿瘤细胞中过表达。免疫毒素候选物被设计为包含对ErbB2具有亲和力的靶向配体以及基于膜溶素的毒素结构域。一种特定的肽候选物NL1.1 - PSA对过表达ErbB2的细胞系表现出选择性细胞毒性。我们利用一种生物工程策略表明，大肠杆菌表达的重组NL1.1 - PSA免疫毒素对过表达ErbB2的细胞也具有选择性细胞毒性。我们的研究结果为在癌症治疗中使用有效的免疫毒素带来了重大希望。
