Nature Communications (Apr 2023)
Anti-cancer pro-inflammatory effects of an IgE antibody targeting the melanoma-associated antigen chondroitin sulfate proteoglycan 4
- Jitesh Chauhan,
- Melanie Grandits,
- Lais C. G. F. Palhares,
- Silvia Mele,
- Mano Nakamura,
- Jacobo López-Abente,
- Silvia Crescioli,
- Roman Laddach,
- Pablo Romero-Clavijo,
- Anthony Cheung,
- Chara Stavraka,
- Alicia M. Chenoweth,
- Heng Sheng Sow,
- Giulia Chiaruttini,
- Amy E. Gilbert,
- Tihomir Dodev,
- Alexander Koers,
- Giulia Pellizzari,
- Kristina M. Ilieva,
- Francis Man,
- Niwa Ali,
- Carl Hobbs,
- Sara Lombardi,
- Daniël A. Lionarons,
- Hannah J. Gould,
- Andrew J. Beavil,
- Jenny L. C. Geh,
- Alastair D. MacKenzie Ross,
- Ciaran Healy,
- Eduardo Calonje,
- Julian Downward,
- Frank O. Nestle,
- Sophia Tsoka,
- Debra H. Josephs,
- Philip J. Blower,
- Panagiotis Karagiannis,
- Katie E. Lacy,
- James Spicer,
- Sophia N. Karagiannis,
- Heather J. Bax
Affiliations
- Jitesh Chauhan
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Melanie Grandits
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Lais C. G. F. Palhares
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Silvia Mele
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Mano Nakamura
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Jacobo López-Abente
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Silvia Crescioli
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Roman Laddach
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Pablo Romero-Clavijo
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Anthony Cheung
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Chara Stavraka
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Alicia M. Chenoweth
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Heng Sheng Sow
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Giulia Chiaruttini
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Amy E. Gilbert
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Tihomir Dodev
- Randall Centre for Cell and Molecular Biophysics, School of Basic and Medical Biosciences, King’s College London
- Alexander Koers
- School of Biomedical Engineering and Imaging Sciences, King’s College London
- Giulia Pellizzari
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Kristina M. Ilieva
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Francis Man
- School of Biomedical Engineering and Imaging Sciences, King’s College London
- Niwa Ali
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London
- Carl Hobbs
- Wolfson Centre for Age-Related Diseases, King’s College London
- Sara Lombardi
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Daniël A. Lionarons
- Oncogene Biology Laboratory, The Francis Crick Institute
- Hannah J. Gould
- Randall Centre for Cell and Molecular Biophysics, School of Basic and Medical Biosciences, King’s College London
- Andrew J. Beavil
- Randall Centre for Cell and Molecular Biophysics, School of Basic and Medical Biosciences, King’s College London
- Jenny L. C. Geh
- Department of Plastic Surgery, Guy’s and St. Thomas’ NHS Foundation Trust
- Alastair D. MacKenzie Ross
- Department of Plastic Surgery, Guy’s and St. Thomas’ NHS Foundation Trust
- Ciaran Healy
- Department of Plastic Surgery, Guy’s and St. Thomas’ NHS Foundation Trust
- Eduardo Calonje
- Dermatopathology Department, St. John’s Institute of Dermatology, St. Thomas’ Hospital
- Julian Downward
- Oncogene Biology Laboratory, The Francis Crick Institute
- Frank O. Nestle
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Sophia Tsoka
- Department of Informatics, Faculty of Natural, Mathematical and Engineering Sciences, King’s College London, Bush House
- Debra H. Josephs
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Philip J. Blower
- School of Biomedical Engineering and Imaging Sciences, King’s College London
- Panagiotis Karagiannis
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Katie E. Lacy
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- James Spicer
- School of Cancer & Pharmaceutical Sciences, King’s College London, Guy’s Hospital
- Sophia N. Karagiannis
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- Heather J. Bax
- St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King’s College London
- DOI
- https://doi.org/10.1038/s41467-023-37811-3
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 18
Abstract
Abstract Outcomes for half of patients with melanoma remain poor despite standard-of-care checkpoint inhibitor therapies. The prevalence of the melanoma-associated antigen chondroitin sulfate proteoglycan 4 (CSPG4) expression is ~70%, therefore effective immunotherapies directed at CSPG4 could benefit many patients. Since IgE exerts potent immune-activating functions in tissues, we engineer a monoclonal IgE antibody with human constant domains recognizing CSPG4 to target melanoma. CSPG4 IgE binds to human melanomas including metastases, mediates tumoricidal antibody-dependent cellular cytotoxicity and stimulates human IgE Fc-receptor-expressing monocytes towards pro-inflammatory phenotypes. IgE demonstrates anti-tumor activity in human melanoma xenograft models engrafted with human effector cells and is associated with enhanced macrophage infiltration, enriched monocyte and macrophage gene signatures and pro-inflammatory signaling pathways in the tumor microenvironment. IgE prolongs the survival of patient-derived xenograft-bearing mice reconstituted with autologous immune cells. No ex vivo activation of basophils in patient blood is measured in the presence of CSPG4 IgE. Our findings support a promising IgE-based immunotherapy for melanoma.
