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Sophia Karagiannis

Name of the laboratory

Reader in Translational Cancer Immunology, Head of Cancer Antibody Discovery and Immunotherapy
St. John's Institute of Dermatology
School of Basic & Medical Biosciences
King's College London, UK

Research Group Members

Members: Antibody Discovery and Immunotherapy
Dr. Sophia Karagiannis
Ms Kristina Ilieva (BCN Research Technician/PhD student, P/T)
Ms Elise French (NHIR/BRC Senior Research Technician)
Dr Heather Bax (Postdoctoral Research Fellow)
Dr Anthony Cheung (BCN Postdoctoral Research Associate)
Dr Silvia Mele (MRC Postdoctoral Research Associate)
Mr Iwan Williams (MRC Postdoctoral Research Assistant)
Dr Silvia Crescioli (NHIR/BRC Postdoctoral Research Associate)
Ms Giulia Pellizzari (King’s Health Schools PhD Student)
Ms Mano Nakamura (Rotary Club/GSTT PhD Student)
Ms Ricadra Melina Hoffmann (NHIR/BRC MRes/PhD Student)
Mr Robert Harris (Cancer Research UK/KHP PhD Student)
Ms Atousa Khiabany (GSTT/Cancer Research UK Technician)

Summary of research

Our main research interests centre on designing antibody therapies for solid tumours such as melanoma, ovarian and breast carcinomas. Our antibody discovery pathway is informed through dissecting humoral immune responses to solid tumours as well as investigating the tumour-targeting mechanisms of IgE class antibodies and Th2 responses in cancer. Patient-derived antibodies and B cell responses are examined as potential biomarkers, with a view of developing stratified medicine approaches and patient-focused treatments. We are presently developing a pipeline of antibodies and our first-in-class agent has reached a Phase I clinical trial.

Research activities

Our laboratory’s activities are focused on the discovery and evaluation of monoclonal antibodies for clinically-challenging solid tumours such as melanoma, ovarian and breast carcinomas and on dissecting immune responses to cancer with particular focus on B cells and the antibodies they produce. Major research streams in our laboratory include: a) dissecting humoral responses and mechanisms of Th-2-biased inflammation in tumours; b) interrogating patient humoral responses as potential biomarkers to aid stratification and with a view of developing patient-focused treatments; c) designing antibodies with potent effector functions; d) elucidating antibody mechanisms of action in disease-relevant models.

Part of our research focuses on the nature and functions of B cells and antibodies in tumour immunity, particularly on tumour-resident and tumour-reactive B cell subsets and on antibody expression in tissues and the circulation. We have recently placed particular emphasis on antibody subclasses with immunosuppressive functions such as IgG4 which may suppress effector cell functions and block cytotoxic antibodies from eradicating cancer. We have demonstrated that antibodies produced in patients with melanoma can recognize and attack tumour cells. Despite producing antibodies recognising tumour cells, patients’ immune systems are mostly ineffective in restricting cancer growth. We have also shown that the tissue environment in tumours provides specific conditions, including production of cytokines like IL-10, which favour expression of IgG4 antibodies, resulting in antibody-mediated immune responses with reduced potency. We furthermore study patient-derived antibodies and B cell responses as potential biomarkers with a view of predicting clinical outcomes and developing patient-focused treatments.

Another key area of research relates to evaluating the impact of antibody class on the therapeutic efficacy of tumour antigen-specific antibodies. We are conducting studies directly comparing the efficacy and mechanisms of action of two different classes of antibodies, IgG and IgE. Our research suggests that compared to IgG, aspects of IgE biology are potentially better suited to cancer therapy, including a higher binding affinity for Fc receptors, and the ability to activate different populations of potent effector cells normally present in tumour tissues to kill tumour cells. Our studies provide an insight into the diversity of mechanisms different classes of antibodies employ to activate immune effector cells such as monocytes/macrophages to target and kill tumours. Our most advanced agent, MOv18 IgE, raised against the α isoform of Folate Receptor, a tumour-associated antigen expressed almost exclusively in tissue cancers such as those of the ovary, breast and skin, has now reached clinical testing and we continue to perform safety, efficacy, potency and mechanistic studies on this agent.

To interrogate antibody potency and mechanisms of action in recruiting, re-educating and activating human effector cell subsets against a range of target antigens, we are developing disease-relevant models featuring engraftment of different components of human immunity. Working with collaborating laboratories and biotechnology partners, we are developing novel antibody glyco-engineering approaches, antibody-drug conjugates, antibodies for further development in imaging studies and for cancer therapy, with the aim of expediting promising therapies and diagnostic tools from the laboratory bench to the patient bedside.

Grant support

Our research has been supported through project and programme grants by the National Institutes of Health Research Biomedical Research Centre, the CR UK New Agents Committee, Breast Cancer Now, the Academy of Medical Sciences, the Biotechnology and Biological Sciences Research Council (BBSRC), the Medical Research Council, the Experimental Cancer Medicine Centre, the CR UK/EPSRC/MRC/NIHR KCL/UCL Comprehensive Cancer Imaging Centre, and the British Skin Foundation.

Publications (2014-present)

* Corresponding author