| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-18 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-023-37811-3 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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