Symposium-in-writing paper

Cancer Immunology, Immunotherapy

, Volume 61, Issue 9, pp 1547-1564

First online:

Recombinant IgE antibodies for passive immunotherapy of solid tumours: from concept towards clinical application

  • Sophia N. KaragiannisAffiliated withNIHR Biomedical Research Centre at Guy’s and St. Thomas’s Hospitals and King’s College LondonCutaneous Medicine and Immunotherapy Unit, St. John’s Institute of Dermatology, Division of Genetics and Molecular Medicine, King’s College London School of Medicine, Guy’s Tower, Guy’s Hospital Email author 
  • , Debra H. JosephsAffiliated withNIHR Biomedical Research Centre at Guy’s and St. Thomas’s Hospitals and King’s College LondonCutaneous Medicine and Immunotherapy Unit, St. John’s Institute of Dermatology, Division of Genetics and Molecular Medicine, King’s College London School of Medicine, Guy’s Tower, Guy’s Hospital
  • , Panagiotis KaragiannisAffiliated withNIHR Biomedical Research Centre at Guy’s and St. Thomas’s Hospitals and King’s College LondonCutaneous Medicine and Immunotherapy Unit, St. John’s Institute of Dermatology, Division of Genetics and Molecular Medicine, King’s College London School of Medicine, Guy’s Tower, Guy’s Hospital
  • , Amy E. GilbertAffiliated withNIHR Biomedical Research Centre at Guy’s and St. Thomas’s Hospitals and King’s College LondonCutaneous Medicine and Immunotherapy Unit, St. John’s Institute of Dermatology, Division of Genetics and Molecular Medicine, King’s College London School of Medicine, Guy’s Tower, Guy’s Hospital
  • , Louise SaulAffiliated withNIHR Biomedical Research Centre at Guy’s and St. Thomas’s Hospitals and King’s College LondonCutaneous Medicine and Immunotherapy Unit, St. John’s Institute of Dermatology, Division of Genetics and Molecular Medicine, King’s College London School of Medicine, Guy’s Tower, Guy’s Hospital
  • , Sarah M. RudmanAffiliated withSection of Research Oncology, Division of Cancer Studies, King’s College London School of Medicine, Guy’s Hospital
  • , Tihomir DodevAffiliated withRandall Division of Cell and Molecular Biophysics, New Hunt’s House, King’s College LondonDivision of Asthma, Allergy and Lung Biology, MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, King’s College London School of Medicine, Guy’s Hospital
  • , Alexander KoersAffiliated withDepartment of Imaging Chemistry & Biology, Division of Imaging Sciences and Biomedical Engineering, King’s College London, The Rayne Institute, St Thomas’ Hospital
  • , Philip J. BlowerAffiliated withDepartment of Imaging Chemistry & Biology, Division of Imaging Sciences and Biomedical Engineering, King’s College London, The Rayne Institute, St Thomas’ Hospital
    • , Christopher CorriganAffiliated withDivision of Asthma, Allergy and Lung Biology, MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, King’s College London School of Medicine, Guy’s Hospital
    • , Andrew J. BeavilAffiliated withRandall Division of Cell and Molecular Biophysics, New Hunt’s House, King’s College LondonDivision of Asthma, Allergy and Lung Biology, MRC and Asthma UK Centre for Allergic Mechanisms of Asthma, King’s College London School of Medicine, Guy’s Hospital
    • , James F. SpicerAffiliated withSection of Research Oncology, Division of Cancer Studies, King’s College London School of Medicine, Guy’s Hospital
    • , Frank O. NestleAffiliated withNIHR Biomedical Research Centre at Guy’s and St. Thomas’s Hospitals and King’s College LondonCutaneous Medicine and Immunotherapy Unit, St. John’s Institute of Dermatology, Division of Genetics and Molecular Medicine, King’s College London School of Medicine, Guy’s Tower, Guy’s Hospital
    • , Hannah J. GouldAffiliated withRandall Division of Cell and Molecular Biophysics, New Hunt’s House, King’s College London

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Abstract

Therapeutic antibodies have revolutionised treatment of some cancers and improved prognosis for many patients. Over half of those available are approved for haematological malignancies, but efficacious antibodies for solid tumours are still urgently needed. Clinically available antibodies belong to the IgG class, the most prevalent antibody class in human blood, while other classes have not been extensively considered. We hypothesised that the unique properties of IgE, a class of tissue-resident antibodies commonly associated with allergies, which can trigger powerful immune responses through strong affinity for their particular receptors on effector cells, could be employed for passive immunotherapy of solid tumours such as ovarian and breast carcinomas. Our laboratory has examined this concept by evaluating two chimaeric antibodies of the same specificity (MOv18) but different isotype, an IgG1 and an IgE against the tumour antigen folate receptor α (FRα). The latter demonstrates the potency of IgE to mount superior immune responses against tumours in disease-relevant models. We identified Fcε receptor-expressing cells, monocytes/macrophages and eosinophils, activated by MOv18 IgE to kill tumour cells by mechanisms such as ADCC and ADCP. We also applied this notion to a marketed therapeutic, the humanised IgG1 antibody trastuzumab and engineered an IgE counterpart, which retained the functions of trastuzumab in restricting proliferation of HER2/neu-expressing tumour cells but also activated effector cells to kill tumour cells by different mechanisms. On-going efficacy, safety evaluations and future first-in-man clinical studies of IgE therapeutics constitute key metrics for this concept, providing new scope for antibody immunotherapies for solid tumours.

Keywords

IgE Tumour immunotherapy FRα/FBP Monocytes/macrophages MOv18 IgE Allergooncology symposium-in-writing HER2/neu IgG Trastuzumab Basophils Eosinophils Mast cells Solid tumours ADCC ADCP Ovarian carcinomas Breast carcinomas