Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma
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 malign...
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Sprache: | English |
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Springer Nature
2024
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| _version_ | 1826317414484148224 |
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| author | Grandclément, C Estoppey, C Dheilly, E Panagopoulou, M Monney, T Dreyfus, C Loyau, J Labanca, V Drake, A De Angelis, S Rubod, A Frei, J Caro, LN Blein, S Martini, E Chimen, M Matthes, T Kaya, Z Edwards, CM Edwards, JR Menoret, E Kervoelen, C Pellat-Deceunynck, C Moreau, P Mbow, ML Srivastava, A Dyson, MR Zhukovsky, EA Perro, M Sammicheli, S |
| author_facet | Grandclément, C Estoppey, C Dheilly, E Panagopoulou, M Monney, T Dreyfus, C Loyau, J Labanca, V Drake, A De Angelis, S Rubod, A Frei, J Caro, LN Blein, S Martini, E Chimen, M Matthes, T Kaya, Z Edwards, CM Edwards, JR Menoret, E Kervoelen, C Pellat-Deceunynck, C Moreau, P Mbow, ML Srivastava, A Dyson, MR Zhukovsky, EA Perro, M Sammicheli, S |
| author_sort | Grandclément, C |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-09-25T04:07:09Z |
| format | Journal article |
| id | oxford-uuid:8043133a-bf8c-4a2e-9952-e96272240015 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2025-02-19T04:38:02Z |
| publishDate | 2024 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:8043133a-bf8c-4a2e-9952-e962722400152025-02-11T11:40:15ZDevelopment of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myelomaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8043133a-bf8c-4a2e-9952-e96272240015EnglishSymplectic ElementsSpringer Nature2024Grandclément, CEstoppey, CDheilly, EPanagopoulou, MMonney, TDreyfus, CLoyau, JLabanca, VDrake, ADe Angelis, SRubod, AFrei, JCaro, LNBlein, SMartini, EChimen, MMatthes, TKaya, ZEdwards, CMEdwards, JRMenoret, EKervoelen, CPellat-Deceunynck, CMoreau, PMbow, MLSrivastava, ADyson, MRZhukovsky, EAPerro, MSammicheli, SAntibody 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. |
| spellingShingle | Grandclément, C Estoppey, C Dheilly, E Panagopoulou, M Monney, T Dreyfus, C Loyau, J Labanca, V Drake, A De Angelis, S Rubod, A Frei, J Caro, LN Blein, S Martini, E Chimen, M Matthes, T Kaya, Z Edwards, CM Edwards, JR Menoret, E Kervoelen, C Pellat-Deceunynck, C Moreau, P Mbow, ML Srivastava, A Dyson, MR Zhukovsky, EA Perro, M Sammicheli, S Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma |
| title | Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma |
| title_full | Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma |
| title_fullStr | Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma |
| title_full_unstemmed | Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma |
| title_short | Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma |
| title_sort | development of isb 1442 a cd38 and cd47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma |
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