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Lookup NU author(s): Professor Gareth Veal
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023, The Author(s).All antibodies approved for cancer therapy are monoclonal IgGs but the biology of IgE, supported by comparative preclinical data, offers the potential for enhanced effector cell potency. Here we report a Phase I dose escalation trial (NCT02546921) with the primary objective of exploring the safety and tolerability of MOv18 IgE, a chimeric first-in-class IgE antibody, in patients with tumours expressing the relevant antigen, folate receptor-alpha. The trial incorporated skin prick and basophil activation tests (BAT) to select patients at lowest risk of allergic toxicity. Secondary objectives were exploration of anti-tumour activity, recommended Phase II dose, and pharmacokinetics. Dose escalation ranged from 70 μg–12 mg. The most common toxicity of MOv18 IgE is transient urticaria. A single patient experienced anaphylaxis, likely explained by detection of circulating basophils at baseline that could be activated by MOv18 IgE. The BAT assay was used to avoid enrolling further patients with reactive basophils. The safety profile is tolerable and maximum tolerated dose has not been reached, with evidence of anti-tumour activity observed in a patient with ovarian cancer. These results demonstrate the potential of IgE therapy for cancer.
Author(s): Spicer J, Basu B, Montes A, Banerji U, Kristeleit R, Miller R, Veal GJ, Corrigan CJ, Till SJ, Figini M, Canevari S, Barton C, Jones P, Mellor S, Carroll S, Selkirk C, Nintos G, Kwatra V, Funingana I-G, Doherty G, Gould HJ, Pellizzari G, Nakamura M, Ilieva KM, Khiabany A, Stavraka C, Chauhan J, Gillett C, Pinder S, Bax HJ, Josephs DH, Karagiannis SN
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2023
Volume: 14
Issue: 1
Online publication date: 25/07/2023
Acceptance date: 22/06/2023
Date deposited: 10/08/2023
ISSN (electronic): 2041-1723
Publisher: Nature Research
URL: https://doi.org/10.1038/s41467-023-39679-9
DOI: 10.1038/s41467-023-39679-9
Data Access Statement: The summary study data are available within this Article, Supplementary Information and Source Data file. The full clinical and laboratory data set that support the findings of this trial are held by Cancer Research Horizons, a wholly owned subsidiary of the trial sponsor Cancer Research UK. Tabulated de-identified patient data (including demographics and adverse event information) will be shared on request from the date of publication and will be retained for 15 years. Access requests are subject to review and approval by Epsilogen (info@epsilogen.com). The study protocol is also available on request from the sponsor (horizons@cancer.org.uk). Source data are provided with this paper.
PubMed id: 37491373
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