Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/25477
Title: Targeted complement activation therapy (TCAT) for cancer treatment
Authors: Doulami, Christiana
Advisors: Kishore, U
Karteris, E
Keywords: Complement System;Cancer;Recombinant fusion proteins;Complement-dependent cytotoxicity (CDC);monoclonal Antibodies
Issue Date: 2022
Publisher: Brunel University London
Abstract: Over the past decades, monoclonal antibody (mAb)-based treatment in cancer has been established as one of the most successful therapies including both hematologic malignancies as well as solid tumors in the biopharmaceutical market. The complement system, a host defense mechanism acting in close collaboration with the innate and adaptive system, has traditionally been considered as an adjunctive component that enhances cytotoxicity of antibody-based therapies. Recent studies have highlighted the important role of complement and therapeutic monoclonal antibodies in cancer therapy. Thus, attempts are being made to understand fully their effector mechanisms and the factors that affect the efficiency of antibodies, in order to enhance complement activity in cancer patients. We have developed a novel broadly applicable mAb platform called targeted ‘complement activation therapy’ (TCAT) that harnesses the full potential of complement to maximize the anti-tumor activity of therapeutic mAbs. Available tumor-targeted therapeutic mAbs fused to various complement proteins or protein subunits were expressed, purified and evaluated for their ability to initiate the complement cascade and their enhanced complement-dependent cytotoxicity (CDC) on target cancer cells. Among many TCAT molecules that were successfully developed, one is able to induce enhanced cytotoxicity levels and eliminate cancer cells efficiently through the initiation of the alternative complement pathway. Additionally, we identified limiting factors and suggest strategies for enhancing further cytotoxicity on the cancer site mediated by the three complement pathways. By achieving efficient cytotoxicity levels through the initiation of the complement cascade this study shows the power of complement system to eliminate cancer and through the TCAT technology we introduce a new therapeutic approach that will improve the outcomes in treatment for cancer patients.
Description: This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University London
URI: https://bura.brunel.ac.uk/handle/2438/25477
Appears in Collections:Biological Sciences
Dept of Life Sciences Theses

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