Design and evaluation of a peptide-based immunotoxin for breast cancer therapeutics

• Chemotherapeutic resistance necessitates the development of new therapeutic options.
• ErbB2 is overexpressed in approximately 30% of breast cancers.
• We present a targeted immunotoxin peptide, termed NL1.1-PSA.
• NL1.1-PSA has specific cytotoxicity toward ErbB2-overexpressing cells.
• We validate a novel genetic engineering strategy for the production of immunotoxin peptides.

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.