Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production

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

doi:10.1080/19420862.2025.2451295

Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	2451295
Journal	Mabs
Volume	17
Issue number	1
DOIs	https://doi.org/10.1080/19420862.2025.2451295
Publication status	Published - 2025

Keywords

AllergoOncology
antibody immunotherapy
basophil activation test
cancer
good manufacturing practice
IgE
investigational medicinal product
MOv18 IgE
process development
production

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10.1080/19420862.2025.2451295

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Bax, H. J., Chauhan, J., McCraw, A. J., Grandits, M., Stavraka, C., Lentfer, H., Hillyer, T., Carroll, S., Vigor, K., Selkirk, C., Figini, M., Cheeseman, J., Urbanowicz, P. A., Gardner, R. A., Spencer, D. I. R., Westwood, N., Mellor, S., Spicer, J., Josephs, D. H., & Karagiannis, S. N. (2025). Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production. Mabs, 17(1), Article 2451295. https://doi.org/10.1080/19420862.2025.2451295

@article{90d0ba18ddbb40079df499771bd66202,

title = "Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production",

abstract = "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.",

keywords = "AllergoOncology, antibody immunotherapy, basophil activation test, cancer, good manufacturing practice, IgE, investigational medicinal product, MOv18 IgE, process development, production",

author = "Bax, {Heather J.} and Jitesh Chauhan and McCraw, {Alexandra J.} and Melanie Grandits and Chara Stavraka and Heike Lentfer and Tim Hillyer and Simon Carroll and Kim Vigor and Chris Selkirk and Mariangela Figini and Jack Cheeseman and Urbanowicz, {Paulina A.} and Gardner, {Richard A.} and Spencer, {Daniel I.R.} and Nigel Westwood and Sarah Mellor and James Spicer and Josephs, {Debra H.} and Karagiannis, {Sophia N.}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Published with license by Taylor & Francis Group, LLC.",

year = "2025",

doi = "10.1080/19420862.2025.2451295",

language = "English",

volume = "17",

journal = "Mabs",

issn = "1942-0862",

publisher = "Landes Bioscience",

number = "1",

}

Bax, HJ, Chauhan, J, McCraw, AJ, Grandits, M , Stavraka, C, Lentfer, H, Hillyer, T, Carroll, S, Vigor, K, Selkirk, C, Figini, M, Cheeseman, J, Urbanowicz, PA, Gardner, RA, Spencer, DIR, Westwood, N, Mellor, S, Spicer, J , Josephs, DH & Karagiannis, SN 2025, 'Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production', Mabs, vol. 17, no. 1, 2451295. https://doi.org/10.1080/19420862.2025.2451295

TY - JOUR

T1 - Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production

AU - Bax, Heather J.

AU - Chauhan, Jitesh

AU - McCraw, Alexandra J.

AU - Grandits, Melanie

AU - Stavraka, Chara

AU - Lentfer, Heike

AU - Hillyer, Tim

AU - Carroll, Simon

AU - Vigor, Kim

AU - Selkirk, Chris

AU - Figini, Mariangela

AU - Cheeseman, Jack

AU - Urbanowicz, Paulina A.

AU - Gardner, Richard A.

AU - Spencer, Daniel I.R.

AU - Westwood, Nigel

AU - Mellor, Sarah

AU - Spicer, James

AU - Josephs, Debra H.

AU - Karagiannis, Sophia N.

PY - 2025

Y1 - 2025

N2 - 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.

AB - 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.

KW - AllergoOncology

KW - antibody immunotherapy

KW - basophil activation test

KW - cancer

KW - good manufacturing practice

KW - IgE

KW - investigational medicinal product

KW - MOv18 IgE

KW - process development

KW - production

UR - http://www.scopus.com/inward/record.url?scp=85215614054&partnerID=8YFLogxK

U2 - 10.1080/19420862.2025.2451295

DO - 10.1080/19420862.2025.2451295

M3 - Article

AN - SCOPUS:85215614054

SN - 1942-0862

VL - 17

JO - Mabs

JF - Mabs

IS - 1

M1 - 2451295

ER -

Physiochemical and functional evaluation of the first-in-class anti-cancer IgE antibody drug, MOv18, through process development and good manufacturing practice production

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Keywords

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