Preparation of Immunotoxin Herceptin-Botulinum and Killing Effects on Two Breast Cancer Cell Lines

Abstract

<b>Background:</b> Worldwide, breast cancer is the most common cancer diagnosed among women and a leadingcause of cancer deaths. The age of onset in Iran has become reduced by a decade for unknown reasons. Herceptin,a humanized monoclonal antibody, is a target therapy for breast cancer cells with over expression of HER2-neu receptors, but it is an expensive drug with only 20% beneficial rate of survival. This study introduces anovel approach to enhance the efficacy of this drug through immunoconjugation of the antibody to botulinumtoxin. Decreasing the cost and adverse effects of the antibody were secondary goals of this study. Materials and<br/><b>Methods</b>: Botulinum toxin was conjugated with Herceptin using heterobifunctional cross linkers, succinimidylacetylthiopropionate (SATP) and sulfo-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC)according to the supplier’s guidelines and tested on two breast cancer cell lines: SK-BR-3 and BT-474. Toxinand Herceptin were also used separately as controls. The cytotoxicity assay was also performed using the newbioconjugate on cultured cells with Alamar blue and a fluorescence plate reader. <br/><b>Results</b>: Herceptin-Toxinbioconjugation significantly improved Herceptin efficacy on both breast cancer cell lines when compared tothe control group. <br/><b>Conclusions</b>: Toxin-Herceptin bioconjugation can be a potential cand