Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production
Antibodies used for cancer therapy are monoclonal IgGs, but tumor-targeting IgE antibodies have shown enhanced effector cell potency against cancer in preclinical models. Research-grade recombinant IgE antibodies have been generated and studied for several decades. The recent Phase 1 clinical trial...
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Taylor & Francis Group
2025-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2025.2451295 |
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| author | Heather J Bax Jitesh Chauhan Alexandra J McCraw Melanie Grandits Chara Stavraka Heike Lentfer Tim Hillyer Simon Carroll Kim Vigor Chris Selkirk Mariangela Figini Jack Cheeseman Paulina A Urbanowicz Richard A Gardner Daniel I R Spencer Nigel Westwood Sarah Mellor James Spicer Debra H Josephs Sophia N Karagiannis |
| author_facet | Heather J Bax Jitesh Chauhan Alexandra J McCraw Melanie Grandits Chara Stavraka Heike Lentfer Tim Hillyer Simon Carroll Kim Vigor Chris Selkirk Mariangela Figini Jack Cheeseman Paulina A Urbanowicz Richard A Gardner Daniel I R Spencer Nigel Westwood Sarah Mellor James Spicer Debra H Josephs Sophia N Karagiannis |
| author_sort | Heather J Bax |
| collection | DOAJ |
| description | Antibodies used for cancer therapy are monoclonal IgGs, but tumor-targeting IgE antibodies have shown enhanced effector cell potency against cancer in preclinical models. Research-grade recombinant IgE antibodies have been generated and studied for several decades. The recent Phase 1 clinical trial of the first-in-class MOv18 IgE, however, necessitated the inaugural process development and scaled manufacture of a recombinant IgE to clinical quality standards. During the process development and scaled Good Manufacturing Practice production, we demonstrate the retention of glycosylation state, biophysical profile, and functional characteristics of MOv18 IgE, including Fc-mediated mast cell degranulation and tumor cell killing. Assessment of manufacturing parameters shows expected pH, purity, concentration, and stability properties, as well as below threshold levels of known biological manufacturing contaminants. We confirm the suitability of the pipeline described for generating intact, functionally active, clinical-grade material for this novel therapeutic class as an Investigational Medicinal Product (IMP), with comparable characteristics to the original research-grade antibody. Furthermore, we screened patient blood ex vivo for potential type I hypersensitivity reaction to MOv18 IgE, using the basophil activation test, to identify patients not predicted to be hypersensitive to MOv18 IgE administration. This study supports the production of functionally active clinical grade (IMP) recombinant IgE and paves the way for the development of a new therapeutic antibody class for a range of antigenic specificities and disease settings. |
| format | Article |
| id | doaj-art-1d0a3528cace409fa159d7df6c84a2a4 |
| institution | Kabale University |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-1d0a3528cace409fa159d7df6c84a2a42025-01-21T03:47:19ZengTaylor & Francis GroupmAbs1942-08621942-08702025-12-0117110.1080/19420862.2025.2451295Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice productionHeather J Bax0Jitesh Chauhan1Alexandra J McCraw2Melanie Grandits3Chara Stavraka4Heike Lentfer5Tim Hillyer6Simon Carroll7Kim Vigor8Chris Selkirk9Mariangela Figini10Jack Cheeseman11Paulina A Urbanowicz12Richard A Gardner13Daniel I R Spencer14Nigel Westwood15Sarah Mellor16James Spicer17Debra H Josephs18Sophia N Karagiannis19St. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, Guy’s Hospital, King’s College London, London, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, Guy’s Hospital, King’s College London, London, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, Guy’s Hospital, King’s College London, London, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, Guy’s Hospital, King’s College London, London, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, Guy’s Hospital, King’s College London, London, UKCentre for Drug Development, Cancer Research UK, London, UKCentre for Drug Development, Cancer Research UK, London, UKCentre for Drug Development, Cancer Research UK, London, UKCentre for Drug Development, Cancer Research UK, London, UKCentre for Drug Development, Cancer Research UK, London, UKANP2, Department of Advanced Diagnostics, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, ItalyLudger, Ltd., Culham Campus, Abingdon, Oxfordshire, UKLudger, Ltd., Culham Campus, Abingdon, Oxfordshire, UKLudger, Ltd., Culham Campus, Abingdon, Oxfordshire, UKLudger, Ltd., Culham Campus, Abingdon, Oxfordshire, UKCentre for Drug Development, Cancer Research UK, London, UKCentre for Drug Development, Cancer Research UK, London, UKSchool of Cancer and Pharmaceutical Sciences, King’s College London, London, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, Guy’s Hospital, King’s College London, London, UKSt. John’s Institute of Dermatology, School of Basic & Medical Biosciences & KHP Centre for Translational Medicine, Guy’s Hospital, King’s College London, London, UKAntibodies used for cancer therapy are monoclonal IgGs, but tumor-targeting IgE antibodies have shown enhanced effector cell potency against cancer in preclinical models. Research-grade recombinant IgE antibodies have been generated and studied for several decades. The recent Phase 1 clinical trial of the first-in-class MOv18 IgE, however, necessitated the inaugural process development and scaled manufacture of a recombinant IgE to clinical quality standards. During the process development and scaled Good Manufacturing Practice production, we demonstrate the retention of glycosylation state, biophysical profile, and functional characteristics of MOv18 IgE, including Fc-mediated mast cell degranulation and tumor cell killing. Assessment of manufacturing parameters shows expected pH, purity, concentration, and stability properties, as well as below threshold levels of known biological manufacturing contaminants. We confirm the suitability of the pipeline described for generating intact, functionally active, clinical-grade material for this novel therapeutic class as an Investigational Medicinal Product (IMP), with comparable characteristics to the original research-grade antibody. Furthermore, we screened patient blood ex vivo for potential type I hypersensitivity reaction to MOv18 IgE, using the basophil activation test, to identify patients not predicted to be hypersensitive to MOv18 IgE administration. This study supports the production of functionally active clinical grade (IMP) recombinant IgE and paves the way for the development of a new therapeutic antibody class for a range of antigenic specificities and disease settings.https://www.tandfonline.com/doi/10.1080/19420862.2025.2451295AllergoOncologyantibody immunotherapybasophil activation testcancergood manufacturing practiceIgE |
| spellingShingle | Heather J Bax Jitesh Chauhan Alexandra J McCraw Melanie Grandits Chara Stavraka Heike Lentfer Tim Hillyer Simon Carroll Kim Vigor Chris Selkirk Mariangela Figini Jack Cheeseman Paulina A Urbanowicz Richard A Gardner Daniel I R Spencer Nigel Westwood Sarah Mellor James Spicer Debra H Josephs Sophia N Karagiannis Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production mAbs AllergoOncology antibody immunotherapy basophil activation test cancer good manufacturing practice IgE |
| title | Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production |
| title_full | Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production |
| title_fullStr | Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production |
| title_full_unstemmed | Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production |
| title_short | Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production |
| title_sort | physiochemical and functional evaluation of the first in class anti cancer ige antibody drug mov18 through process development and good manufacturing practice production |
| topic | AllergoOncology antibody immunotherapy basophil activation test cancer good manufacturing practice IgE |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2025.2451295 |
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