title: Design and evaluation of a peptide-based immunotoxin for breast cancer therapeutics.
abstract: 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.
authors: Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA.
authors: Kelsey J
authors: KJ
authors: Weigel
authors: Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA.
authors: Luqun
authors: L
authors: Shen
authors: Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA.
authors: Clayton L
authors: CL
authors: Thomas
authors: Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA.
authors: Daniel
authors: D
authors: Alber
authors: Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA.
authors: Lauren
authors: L
authors: Drapalik
authors: 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.
authors: Zachary T
authors: ZT
authors: Schafer
authors: 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.
authors: Shaun W
authors: SW
authors: Lee
keywords: Breast cancer; EGF, epidermal growth factor; ErbB2-positive; IL-2, interleukin 2; Immunotoxin; MBP, maltose binding protein; Therapeutics