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Preparation of Immunotoxin Herceptin-Botulinum and Killing Effects on Two Breast Cancer Cell Lines
Saieh Hajighasemlou1, Mahmoud Alebouyeh, Hossein Rastegar
1Iran Food and Drug Administration, Tehran, Iran
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.
Materials And 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.
Insights
This study enhanced Herceptin efficacy for HER2-positive breast cancer by conjugating it with botulinum toxin. The novel bioconjugate shows increased efficiency in preclinical models.
Area of Science:
- Oncology
- Biotechnology
- Pharmacology
Background:
- Breast cancer is a leading cause of death in women globally.
- Herceptin is an effective but expensive targeted therapy for HER2-positive breast cancer, with limited survival benefits.
- The study addresses the need for more effective and potentially less costly breast cancer treatments.
Purpose of the Study:
- To develop a novel immunoconjugate by combining Herceptin with botulinum toxin.
- To enhance the therapeutic efficacy of Herceptin for HER2-positive breast cancer.
- To explore potential reductions in cost and adverse effects associated with Herceptin treatment.
Main Methods:
- Botulinum toxin was chemically conjugated to Herceptin using heterobifunctional crosslinkers (SATP and SMCC).
- The efficacy of the Herceptin-Toxin bioconjugate was evaluated on SK-BR-3 and BT-474 breast cancer cell lines.
- Cytotoxicity was assessed using the Alamar blue assay and a fluorescence plate reader.
Main Results:
- The Herceptin-Toxin bioconjugate demonstrated significantly improved efficacy compared to Herceptin alone.
- Enhanced therapeutic effect was observed in both tested breast cancer cell lines (SK-BR-3 and BT-474).
Conclusions:
- Toxin-Herceptin bioconjugation represents a promising strategy for enhancing breast cancer treatment.
- This approach offers potential for increased efficiency in managing HER2-receptor-overexpressing breast cancers.
- Further investigation may lead to improved therapeutic options for breast cancer patients.
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