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Unlocking the Power of Complement-Dependent Cytotoxicity: Engineering Strategies for the Development of Potent Therapeutic Antibodies for Cancer Treatments

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Abstract

The complement system is a crucial part of the innate immune response, providing defense against invading pathogens and cancer cells. Recently, it has become evident that the complement system plays a significant role in anticancer activities, particularly through complement-dependent cytotoxicity (CDC), alongside antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP). With the discovery of new roles for serum complement molecules in the human immune system, various approaches are being pursued to develop CDC-enhanced antibody therapeutics. In this review, we focus on successful antibody engineering strategies for enhancing CDC, analyzing the lessons learned and the limitations of each approach. Furthermore, we outline potential pathways for the development of antibody therapeutics specifically aimed at enhancing CDC for superior therapeutic efficacy in the future.

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Authors and Affiliations

  1. Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seoul, 02841, Republic of Korea

    Wonju Lee, Sang Min Lee & Sang Taek Jung

  2. Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea

    Wonju Lee & Sang Taek Jung

  3. Department of Applied Chemistry, Kookmin University, Seoul, 02707, Republic of Korea

    Sang Min Lee

  4. Biomedical Research Center, Korea University Anam Hospital, Seoul, 02841, Republic of Korea

    Sang Taek Jung

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This research was supported by the Korea Drug Development Fund funded by the Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (HN21C0103, Republic of Korea). We are also grateful for support from grants from the Basic Science Research Program (RS-2023-00245059 and 2022R1A4A2000827) through the National Research Foundation of Korea funded by the Ministry of Science and ICT.

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Wonju Lee, Sang Min Lee, and Sang Taek Jung declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Lee, W., Lee, S.M. & Jung, S.T. Unlocking the Power of Complement-Dependent Cytotoxicity: Engineering Strategies for the Development of Potent Therapeutic Antibodies for Cancer Treatments. BioDrugs 37, 637–648 (2023). https://doi.org/10.1007/s40259-023-00618-1

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