title: Preparation of Immunotoxin Herceptin-Botulinum and Killing Effects on Two Breast Cancer Cell Lines.
abstract: BACKGROUND
  Worldwide, breast cancer is the most common cancer diagnosed among women and a leading cause 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 a novel approach to enhance the efficacy of this drug through immunoconjugation of the antibody to botulinum toxin. Decreasing the cost and adverse effects of the antibody were secondary goals of this study.
  
  
  METHODS
  Botulinum toxin was conjugated with Herceptin using heterobifunctional cross linkers, succinimidyl acetylthiopropionate (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. Toxin and Herceptin were also used separately as controls. The cytotoxicity assay was also performed using the new bioconjugate on cultured cells with Alamar blue and a fluorescence plate reader.
  
  
  RESULTS
  Herceptin-Toxin bioconjugation significantly improved Herceptin efficacy on both breast cancer cell lines when compared to the control group.
  
  
  CONCLUSIONS
  Toxin-Herceptin bioconjugation can be a potential candidate with increased efficiency for treating breast cancer patients with over expression of the HER2 receptor.
authors: Iran Food and Drug Administration, Tehran, Iran E-mail : mahdiy@yahoo.com.
authors: Saieh
authors: S
authors: Hajighasemlou
authors: Mahmoud
authors: M
authors: Alebouyeh
authors: Hossein
authors: H
authors: Rastegar
authors: Mojgan Taghizadeh
authors: MT
authors: Manzari
authors: Milad
authors: M
authors: Mirmoghtadaei
authors: Behjat
authors: B
authors: Moayedi
authors: Maryam
authors: M
authors: Ahmadzadeh
authors: Farzad
authors: F
authors: Parvizpour
authors: Behrooz
authors: B
authors: Johari
authors: Maria Moslemi
authors: MM
authors: Naeini
authors: Mohammad M
authors: MM
authors: Farajollahi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001905:Botulinum Toxins / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D009498:Neurotoxins / Q000737:chemistry / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D000068878:Trastuzumab / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001905:Botulinum Toxins; D003432:Cross-Linking Reagents; D009498:Neurotoxins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human