In Silico Pertuzumab Antibody Affinity Maturation to Improve Breast Cancer Immunotherapy

Introduction & Aim: Breast cancer is one of the most common types of cancer which is one of the leading causes of the high mortality rate among women. Cancer immunotherapy has emerged as a promising approach to treatment of cancer. Pertuzumab is a monoclonal antibody used in combination with trastuzumab and docetaxel for the treatment of metastatic HER2-positive breast cancer. For a successful cancer immunotherapy the different features of therapeutic antibodies such as binding affinity should be improved. In this regard, we have lunched an in silico approach to increase the affinity of pertuzumab to HER2. Methods: We find the important amino acids of the pertuzumab antibody using different software and web servers, and then we replaced these amino acids with others to improve antibody binding affinity. Finally, we examined the binding affinity of antibody variants to antigens using different docking programs. Results: The results indicated that the replaced new amino acids in the binding site of pertuzumab increase the affinity of the antibody to HER2. Conclusion: In conclusion it should be pointed out that, the employed in silico approach could pave the way for increasing the affinity of antibodies. Increased affinity enhances the biological action of the antibody, which in turn improves the therapeutic effects. Furthermore, the increased antibody affinity can reduce the therapeutic dose of the antibody, resulting in lower toxicity and handling cost.