Studying the effect of microbial infections on the molecular actions of therapeutic monoclonal antibodies on certain tissue culture cell lines / Mai Mohammed Gamal Esmail Allam ; Supervised Manal Mohamed Maher , Ahmed Sherif Attia , Nahla Shehata Kotb

Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Microbiology and Immunology

Monoclonal antibodies (mAbs) are antibodies of a single antigen specificity produced by identical immune cells. They act by several mechanisms of action for example: Epidermal growth factor receptors (EGFR) blockers which block growth signals.Cetuximab is an (EGFR) blocker immunoglobulin (Ig) G1 human murine chimeric. Cetuximab alone or in combination with cytotoxic chemotherapy is used as a treatment for patients with colorectal cancer (CRC) which is the third most commonly diagnosed malignancy. In addition, it is the third leading cause of cancer-related deaths in the world, and its burden is expected to increase by 60% to more than 2.2 million new cases and 1.1 million cancer deaths by 2030. In many instances, cancer patients acquire infections whileunder treatment. How microbial infection would interact with the therapeutic mAbs is not clearly known.Accordingly, the current study focused on studying the effect of S. aureus, S. epidermidis or Vesicular stomatitis virus (VSV) on the activity of Cetuximab on the human colon cancer cell line HCT116. Using the MTT colorimetric assay, it was shown that indeed microbial infection exaggerates the cytotoxic activity of Cetuximab. In addition, the molecular mechanism behind this synergistic cytotoxic activity was investigated using RT-RT-PCR through gene expression analyses of the key players' genes in the apoptotic pathway (bax and bcl-2 genes)

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