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Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trial

Spicer, James; Basu, Bristi; Montes, Ana; Banerji, Udai; Kristeleit, Rebecca; Miller, Rowan; Veal, Gareth JJ; ... Karagiannis, Sophia NN; + view all (2023) Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trial. Nature Communications , 14 (1) , Article 4180. 10.1038/s41467-023-39679-9. Green open access

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Abstract

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.

Type: Article
Title: Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trial
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-023-39679-9
Publisher version: https://doi.org/10.1038/s41467-023-39679-9
Language: English
Additional information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, MONOCLONAL-ANTIBODY, OVARIAN-CANCER, DEPENDENT CYTOTOXICITY, CLINICAL-TRIALS, CELLS, IMMUNOTHERAPY, SURVEILLANCE, ANAPHYLAXIS, MECHANISMS
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre
URI: https://discovery.ucl.ac.uk/id/eprint/10182533
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