Abstract 347: Developing a novel immunotoxin that targets cells overexpressing ErbB2

• Published in: Cancer research (Chicago, Ill.) Ill.), 2016-07, Vol.76 (14_Supplement), p.347-347
• Main Authors: Shen, Luqun, Weigel, Kelsey, Thomas, Clayton, Drapalik, Lauren, Schafer, Zachary T., Lee, Shaun
• Format: Article
• Language: English
• Subjects: Escherichia coli
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2016-347

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. The use of a membrane lysin as the toxin domain distinguishes our immunotoxins from numerous others in that internalization of the toxin is not required to induce cell death. 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. While Herceptin treatment has been effective in patients with ErbB2 positive breast cancer, our novel immunotoxin may ultimately prove to be a novel and efficacious addition to the arsenal of approaches used to eliminate Herceptin-resistant breast cancer cells. Citation Format: Luqun Shen, Kelsey Weigel, Clayton Thomas, Lauren Drapalik, Zachary T. Schafer, Shaun Lee. Developing a novel immunotoxin that targets cells overexpressing ErbB2. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 347.