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Chauhan, Jitesh; Grandits, Melanie; Palhares, Lais C. G. F.; Mele, Silvia; Nakamura, Mano; López-Abente, Jacobo; Crescioli, Silvia; Laddach, Roman; Romero-Clavijo, Pablo; Cheung, Anthony; Stavraka, Chara; Chenoweth, Alicia M.; Sow, Heng Sheng; Chiaruttini, Giulia; Gilbert, Amy E.; Dodev, Tihomir; Koers, Alexander; Pellizzari, Giulia; Ilieva, Kristina M.; Man, Francis; Ali, Niwa; Hobbs, Carl; Lombardi, Sara; Lionarons, Daniël A.; [...]

Anti-cancer pro-inflammatory effects of an IgE antibody targeting the melanoma-associated antigen chondroitin sulfate proteoglycan 4

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  • Medientyp: E-Artikel
  • Titel: Anti-cancer pro-inflammatory effects of an IgE antibody targeting the melanoma-associated antigen chondroitin sulfate proteoglycan 4
  • Beteiligte: Chauhan, Jitesh; Grandits, Melanie; Palhares, Lais C. G. F.; Mele, Silvia; Nakamura, Mano; López-Abente, Jacobo; Crescioli, Silvia; Laddach, Roman; Romero-Clavijo, Pablo; Cheung, Anthony; Stavraka, Chara; Chenoweth, Alicia M.; Sow, Heng Sheng; Chiaruttini, Giulia; Gilbert, Amy E.; Dodev, Tihomir; Koers, Alexander; Pellizzari, Giulia; Ilieva, Kristina M.; Man, Francis; Ali, Niwa; Hobbs, Carl; Lombardi, Sara; Lionarons, Daniël A.; [...]
  • Erschienen: Springer Science and Business Media LLC, 2023
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/s41467-023-37811-3
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>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.</jats:p>
  • Zugangsstatus: Freier Zugang