Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma.

Autor: Grandclément C; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Estoppey C; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Dheilly E; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Panagopoulou M; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Monney T; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Dreyfus C; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Loyau J; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Labanca V; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Drake A; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., De Angelis S; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Rubod A; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Frei J; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Caro LN; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Blein S; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Martini E; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Chimen M; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Matthes T; Haematology Service, Department of Oncology and Clinical Pathology Service, Department of Diagnostics, University Hospital Geneva, 1211, Geneva, Switzerland., Kaya Z; Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Institute, University of Oxford, Oxford, UK., Edwards CM; Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Institute, University of Oxford, Oxford, UK., Edwards JR; Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Institute, University of Oxford, Oxford, UK., Menoret E; Nantes Université, Inserm, CNRS, Université d'Angers, CRCI2NA, Nantes, France., Kervoelen C; Nantes Université, Inserm, CNRS, Université d'Angers, CRCI2NA, Nantes, France., Pellat-Deceunynck C; Nantes Université, Inserm, CNRS, Université d'Angers, CRCI2NA, Nantes, France.; SIRIC ILIAD, Angers, Nantes, France., Moreau P; Nantes Université, Inserm, CNRS, Université d'Angers, CRCI2NA, Nantes, France.; SIRIC ILIAD, Angers, Nantes, France.; Service d'Hématologie Clinique, Unité d'Investigation Clinique, CHU, Nantes, France., Mbow ML; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Srivastava A; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Dyson MR; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Zhukovsky EA; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland., Perro M; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland. mario.perro@iginnovate.com., Sammicheli S; Ichnos Glenmark Innovation, Lausanne, CH, Switzerland. stefano.sammicheli@iginnovate.com.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Mar 06; Vol. 15 (1), pp. 2054. Date of Electronic Publication: 2024 Mar 06.
DOI: 10.1038/s41467-024-46310-y
Abstrakt: Antibody engineering can tailor the design and activities of therapeutic antibodies for better efficiency or other advantageous clinical properties. Here we report the development of ISB 1442, a fully human bispecific antibody designed to re-establish synthetic immunity in CD38+ hematological malignancies. ISB 1442 consists of two anti-CD38 arms targeting two distinct epitopes that preferentially drive binding to tumor cells and enable avidity-induced blocking of proximal CD47 receptors on the same cell while preventing on-target off-tumor binding on healthy cells. The Fc portion of ISB 1442 is engineered to enhance complement dependent cytotoxicity, antibody dependent cell cytotoxicity and antibody dependent cell phagocytosis. ISB 1442 thus represents a CD47-BsAb combining biparatopic targeting of a tumor associated antigen with engineered enhancement of antibody effector function to overcome potential resistance mechanisms that hamper treatment of myeloma with monospecific anti-CD38 antibodies. ISB 1442 is currently in a Phase I clinical trial in relapsed refractory multiple myeloma.
(© 2024. The Author(s).)
Databáze: MEDLINE
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