Name of the laboratory
- Reader in Translational Cancer Immunology, Head of Cancer Antibody Discovery and Immunotherapy
- St. John's Institute of Dermatology
- Division of Genetics and Molecular Medicine
- Faculty of Life Sciences and Medicine
- King's College London, UK
Research Group Members
Dr. Sophia Karagiannis firstname.lastname@example.org
Ms Kristina Ilieva (Research Technician/PhD student, P/T)
Dr Isabel Correa (NHIR/BRC Senior Research Technician)
Dr Heather Bax (Postdoctoral Research Associate)
Dr Debra H Josephs (Clinical Lecturer, Oncology)
Dr Anthony Cheung (Postdoctoral Research Associate)
Dr Silvia Mele (Postdoctoral Research Associate)
Dr Giulia Chiaruttini (Postdoctoral Research Assistant)
Dr Silvia Crescioli (NHIR/BRC Postdoctoral Research Associate)
Ms Giulia Pellizzari (Health Schools PhD Student)
Ms Mano Nakamura (Rotary Club/GSTT PhD Student)
Ms Ricadra Melina Hoffmann (NHIR/BRC MRes/PhD Student)
Summary of research
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. We are furthermore evaluating a panel of antibodies for radionuclide imaging studies and for cancer therapy, with the aim of expediting promising therapies and diagnostic tools from the laboratory bench to the patient bedside.
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, the Experimental Cancer Medicine Centre, the Medical Research Council, the CR UK/EPSRC/MRC/NIHR KCL/UCL Comprehensive Cancer Imaging Centre, Breast Cancer Now, the Academy of Medical Sciences and the British Skin Foundation.
- Vigor K, Emerson J, Scott R, Cheek J, Barton C, Bax HJ, Josephs DH, Karagiannis SN, Spicer JF, Lentfer H. Development of Downstream Processing to Minimise Beta-Glucan Impurities in GMP-Manufactured Therapeutic Antibodies. Biotechnol Prog. 2016; 10.1002/btpr.2359
- Bax HJ, Josephs DH, Pellizzari G, Spicer JF, Montes A, Karagiannis SN*. Therapeutic targets and new directions for antibodies developed for ovarian cancer. MAbs. 2016; 10.1080/19420862.2016.1219005:0.
- Barton C, Vigor K, Scott R, Jones P, Lentfer H, Bax HJ, Josephs DH, Karagiannis SN, Spicer JF. Beta-glucan contamination of pharmaceutical products: How much should we accept? Cancer Immunol Immunother. 2016; 10.1007/s00262-016-1875-9.
- Wulaningsih W, Holmberg L, Garmo H, Karagiannis SN, Ahlstedt S, Malmstrom H, Lambe M, Hammar N, Walldius G, Jungner I, Ng T, Van Hemelrijck M. Investigating the association between allergen-specific immunoglobulin E, cancer risk and survival. Oncoimmunology. 2016; 5(6):e1154250.
- Saul L, Ilieva KM, Bax HJ, Karagiannis P, Correa I, Rodriguez-Hernandez I, Josephs DH, Tosi I, Egbuniwe IU, Lombardi S, Crescioli S, Hobbs C, Villanova F, Cheung A, Geh JL, Healy C, Harries M, Sanz-Moreno V, Fear DJ, Spicer JF, Lacy KE, Nestle FO, Karagiannis SN*. IgG subclass switching and clonal expansion in cutaneous melanoma and normal skin. Sci Rep. 2016; 6:29736.
- Cheung A, Bax HJ, Josephs DH, Ilieva KM, Pellizzari G, Opzoomer J, Bloomfield J, Fittall M, Grigoriadis A, Figini M, Canevari S, Spicer JF, Tutt AN, Karagiannis SN*. Targeting folate receptor alpha for cancer treatment. Oncotarget. 2016; 10.18632/oncotarget.9651.
- Crescioli S, Correa I, Karagiannis P, Davies AM, Sutton BJ, Nestle FO, Karagiannis SN*. IgG4 Characteristics and Functions in Cancer Immunity. Curr Allergy Asthma Rep. 2016; 16(1):7.
- Cantelli G, Orgaz JL, Rodriguez-Hernandez I, Karagiannis P, Maiques O, Matias-Guiu X, Nestle FO, Marti RM, Karagiannis SN, Sanz-Moreno V. TGF-beta-Induced Transcription Sustains Amoeboid Melanoma Migration and Dissemination. Curr Biol. 2015; 25(22):2899-2914.
- Karagiannis P, Villanova F, Josephs DH, Correa I, Van Hemelrijck M, Hobbs C, Saul L, Egbuniwe IU, Tosi I, Ilieva KM, Kent E, Calonje E, Harries M, Fentiman I, Taylor-Papadimitriou J, Burchell J, Spicer JF, Lacy KE, Nestle FO, Karagiannis SN*. Elevated IgG4 in patient circulation is associated with the risk of disease progression in melanoma. Oncoimmunology. 2015; 4(11):e1032492.
- Josephs DH, Bax HJ, Lentfer H, Selkirk C, Spicer JF, Karagiannis SN*. Potential for monocyte recruitment by IgE immunotherapy for cancer in a rat model of tumour metastasis. Lancet. 2015; 385 Suppl 1:S53.
- Egbuniwe IU, Karagiannis SN, Nestle FO, Lacy KE. Revisiting the role of B cells in skin immune surveillance. Trends Immunol. 2015; 36(2):102-111.
- Josephs DH, Bax HJ, Karagiannis SN*. Tumour-associated macrophage polarisation and re-education with immunotherapy. Front Biosci (Elite Ed). 2015; 7:293-308.
- Karagiannis SN*, Lacy KE. New tools to treat malignant melanoma. Nursing in Practice. 2015;84, 20 May 2015.
- Karagiannis P, Fittall M, Karagiannis SN*. Evaluating biomarkers in melanoma. Front Oncol. 2014; 4:383.
- Ilieva KM, Correa I, Josephs DH, Karagiannis P, Egbuniwe IU, Cafferkey MJ, Spicer JF, Harries M, Nestle FO, Lacy KE, Karagiannis SN*. Effects of BRAF mutations and BRAF inhibition on immune responses to melanoma. Mol Cancer Ther. 2014; 13(12):2769-2783.
- Dodev TS, Karagiannis P, Gilbert AE, Josephs DH, Bowen H, James LK, Bax HJ, Beavil R, Pang MO, Gould HJ, Karagiannis SN*, Beavil AJ. A tool kit for rapid cloning and expression of recombinant antibodies. Sci Rep. 2014; 4:5885.
- Malas S, Harrasser M, Lacy KE, Karagiannis SN*. Antibody therapies for melanoma: new and emerging opportunities to activate immunity (Review). Oncol Rep. 2014; 32(3):875-886.
- Orgaz JL, Pandya P, Dalmeida R, Karagiannis P, Sanchez-Laorden B, Viros A, Albrengues J, Nestle FO, Ridley AJ, Gaggioli C, Marais R, Karagiannis SN, Sanz-Moreno V. Diverse matrix metalloproteinase functions regulate cancer amoeboid migration. Nat Commun. 2014; 5:4255.
- Cohen ES, Dobson CL, Kack H, Wang B, Sims DA, Lloyd CO, England E, Rees DG, Guo H, Karagiannis SN, O'Brien S, Persdotter S, Ekdahl H, Butler R, Keyes F, Oakley S, Carlsson M, Briend E, Wilkinson T, Anderson IK, Monk PD, von Wachenfeldt K, Eriksson PO, Gould HJ, Vaughan TJ, May RD. A novel IgE-neutralizing antibody for the treatment of severe uncontrolled asthma. MAbs. 2014; 6(3):756-764.
- Saul L, Josephs DH, Cutler K, Bradwell A, Karagiannis P, Selkirk C, Gould HJ, Jones P, Spicer JF, Karagiannis SN*. Comparative reactivity of human IgE to cynomolgus monkey and human effector cells and effects on IgE effector cell potency. MAbs. 2014; 6(2):509-522.
- Josephs DH, Spicer JF, Karagiannis P, Gould HJ, Karagiannis SN*. IgE immunotherapy: a novel concept with promise for the treatment of cancer. MAbs. 2014; 6(1):54-72.
- Josephs DH, Spicer JF, Corrigan CJ, Gould HJ, Karagiannis SN*. Epidemiological associations of allergy, IgE and cancer. Clin Exp Allergy. 2013; 43(10):1110-1123.
- Karagiannis SN*, Karagiannis P, Josephs DH, Saul L, Gilbert AE, Upton N, Gould HJ. Immunoglobulin E and Allergy: Antibodies in Immune Inflammation and Treatment. Microbiol Spectr. 2013; 1(1).
- Karagiannis P, Gilbert AE, Nestle FO, Karagiannis SN*. IgG4 antibodies and cancer-associated inflammation: Insights into a novel mechanism of immune escape. Oncoimmunology. 2013; 2(7):e24889.
- Karagiannis P, Gilbert AE, Josephs DH, Ali N, Dodev T, Saul L, Correa I, Roberts L, Beddowes E, Koers A, Hobbs C, Ferreira S, Geh JL, Healy C, Harries M, Acland KM, Blower PJ, Mitchell T, Fear DJ, Spicer JF, Lacy KE, Nestle FO, Karagiannis SN*. IgG4 subclass antibodies impair antitumor immunity in melanoma. J Clin Invest. 2013; 123(4):1457-1474.
- Karagiannis S*, Beavil A, Nestle F. IgE anti-HMW-MAA antibody. Patent Application, 2013; PCT/GB2011/051884; WO2013050725 A1, CA2848842A1, EP2764025A1, US20140322246. Available from: https://www.google.com/patents/WO2013050725A1?cl=en.
- Tsoka S, Ainali C, Karagiannis P, Josephs DH, Saul L, Nestle FO, Karagiannis SN*. Toward prediction of immune mechanisms and design of immunotherapies in melanoma. Crit Rev Biomed Eng. 2012; 40(4):279-294.
- Lacy KE, Karagiannis SN, Nestle FO. Advances in the treatment of melanoma. Clin Med (Lond). 2012; 12(2):168-171.
- Chu CC, Ali N, Karagiannis P, Di Meglio P, Skowera A, Napolitano L, Barinaga G, Grys K, Sharif-Paghaleh E, Karagiannis SN, Peakman M, Lombardi G, Nestle FO. Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation. J Exp Med. 2012; 209(5):935-945.
- Karagiannis SN*, Josephs DH, Karagiannis P, Gilbert AE, Saul L, Rudman SM, Dodev T, Koers A, Blower PJ, Corrigan C, Beavil AJ, Spicer JF, Nestle FO, Gould HJ. Recombinant IgE antibodies for passive immunotherapy of solid tumours: from concept towards clinical application. Cancer Immunol Immunother. 2012; 61(9):1547-1564.
- Lacy KE, Karagiannis SN, Nestle FO. Immunotherapy for melanoma. Expert Rev Dermatol. 2012; 7(1):51-68.
* Corresponding author
- CroatiaStipan JonjicUniversity of Rijeka
- FranceAndré PèlegrinInstitut de Recherche en Cancérologie de Montpellier, IRCM
- FranceArmand BensussanHôpital Saint Louis
- FrancePierre LafayeInstitut Pasteur
- GermanyFriedrich Koch-NolteUniversity Medical Center Hamburg-Eppendorf
- HungaryJohanna SymmonsEnglish & Scientific Consulting Kft. (SCICONS)
- HungaryPeter BaloghClinical Center, University of Pecs
- ItalyFabio MalavasiUniversity of Torino Medical School
- RussiaAlexander TaraninInstitute of Molecular and Cellular Biology
- RussiaAlexander FilatovInstitute of Immunology
- SloveniaVladka Čurin ŠerbecBlood Trasfusion Centre of Slovenia
- SpainGiovanna RoncadorCentro Nacional de Investigaciones Oncológicas
- SpainJosé I. Rodríguez BarbosaInstituto Universitario de Biomedicina
- SpainLeonor KremerCentro Nacional de Biotecnología/CSIC
- SpainNúria PascualNb4D
- SpainPablo EngelMedical School, University of Barcelona
- United KingdomUniversity of OxfordLRF Haemato-oncology Group
- United KingdomVertebrate Antibodies Limited (VAL)
- United KingdomUniversity of OxfordOxFabs
- United KingdomKing's College LondonSt. John's Institute of Dermatology