Year: 2026
Type: article
Abstract: Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, highlighting the need for durable therapies. Natural killer (NK) cell engagers (NKCEs) represent a promising alternative to T cell therapies, offering potent anti-tumor activity with limited cytokine release. SAR445514 (SAR'514) is a trifunctional NKCE that co-engages NKp46 and FcγRIIIa to activate NK cells while targeting B cell maturation antigen (BCMA) on MM cells. After exploring several molecular formats with varied BCMA and NKp46 valency, we selected SAR'514, a monovalent format with enhanced antibody-dependent cellular cytotoxicity (ADCC). SAR'514 has potent and selective anti-tumor activity in vitro and in vivo, outperforming other FcγRIIIa-immune cell engagers, while inducing minimal cytokine release compared to T cell engagers targeting the same antigen. Ex vivo, SAR'514 efficiently activates NK cells from MM patients and induces cytotoxicity against autologous malignant cells, including those resistant to standard therapies. These findings support further development of SAR'514.
Source: Cell Reports Medicine
Authors: Alexandre Tang, Laurent Gauthier, Elisa Zaghi, Jochen Beninga, Céline Amara, Alexandra Basset, Benjamin Rossi, Dorothée Bourges, Céline Nicolazzi, Pauline Rettman, Valérie Couturier, Norbert Zombori, Laura Mendez, Yu Qiu, Joseph Batchelor, Audrey Blanchard-Alvarez, Franceline Guillot, Marilyn Giordano, Nicolas Gourdin, Ariane Morel, Cyrille Touzeau, Catherine Pellat-Deceunynck, Emilie Narni-Mancinelli, Yannis Morel, Valeria Fantin, Eric Vivier, Angela Virone-Oddos, Marielle Chiron
Institutions: Sanofi (France), Innate Pharma (France), Sanofi (Germany), Centre National de la Recherche Scientifique, Inserm, Centre Hospitalier Universitaire de Nantes, Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers, Nantes Université, Aix-Marseille Université, Centre d’Immunologie de Marseille-Luminy, Hôpital de la Timone, Prédicteurs moléculaires et nouvelles cibles en oncologie
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: Centre d'immunologie de Marseille-Luminy, Sanofi, Aix-Marseille Université, European Commission, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Labex, Centre National de la Recherche Scientifique, Canceropôle PACA, Institut National Du Cancer, Institut Gustave-Roussy, Fondation Gustave Roussy, European Research Council, Innate Pharma
OpenAlex ID: W7129208622