Open AccessDesign and evaluation of a peptide‐based immunotoxin for breast cancer therapeutics
Author(s) -
Weigel Kelsey J.,
Shen Luqun,
Thomas Clayton L.,
Alber Daniel,
Drapalik Lauren,
Schafer Zachary T.,
Lee Shaun W.
Publication year - 2015
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1016/j.fob.2015.03.005
Subject(s) - immunotoxin , cytotoxicity , cancer research , fusion protein , cytotoxic t cell , peptide , recombinant dna , tyrosine kinase , receptor tyrosine kinase , chemistry , receptor , biology , pharmacology , in vitro , biochemistry , gene
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.