@article{9bc1cafcb1a5456ea4c18d509f6edb59,
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",
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.",
keywords = "Female, Humans, Immunoglobulin E, Antibodies, Monoclonal/adverse effects, Ovarian Neoplasms, Basophils, Folic Acid",
author = "James Spicer and Bristi Basu and Ana Montes and Udai Banerji and Rebecca Kristeleit and Rowan Miller and Veal, {Gareth J} and Corrigan, {Christopher J} and Till, {Stephen J} and Mariangela Figini and Silvana Canevari and Claire Barton and Paul Jones and Sarah Mellor and Simon Carroll and Chris Selkirk and George Nintos and Vineet Kwatra and Ionut-Gabriel Funingana and Gary Doherty and Gould, {Hannah J} and Giulia Pellizzari and Mano Nakamura and Ilieva, {Kristina M} and Atousa Khiabany and Chara Stavraka and Jitesh Chauhan and Cheryl Gillett and Sarah Pinder and Bax, {Heather J} and Josephs, {Debra H} and Karagiannis, {Sophia N}",
note = "Funding Information: The trial was funded and sponsored by Cancer Research UK, who collaborated with the academic authors in designing the trial, collated the clinical data, and reviewed the manuscript. The authors acknowledge additional financial support from the UK Department of Health and Cancer Research UK via Experimental Cancer Medicine Centre and NIHR Biomedical Research Centre grants to King{\textquoteright}s Health Partners/Guy{\textquoteright}s & St Thomas{\textquoteright} NHS Foundation Trust (JS), the University of Cambridge/Cambridge University Hospitals NHS Foundation Trust (BB), University College London/UCL Hospital NHS Trust (RM), and Institute of Cancer Research/Royal Marsden Hospital (UB). We acknowledge the Immune Monitoring Core Facility team at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust (IS-BRC-1215-20006) for flow cytometry facilities, and the Cancer Research UK King{\textquoteright}s Health Partners Centre at King{\textquoteright}s College London (C604/A25135). The authors would like to thank the patients, their families, the clinical research teams, as well as Sharmistha Ghosh, Amy Pope and Natalie Woodman for their contribution to this study. Funding Information: The trial was funded and sponsored by Cancer Research UK, who collaborated with the academic authors in designing the trial, collated the clinical data, and reviewed the manuscript. The authors acknowledge additional financial support from the UK Department of Health and Cancer Research UK via Experimental Cancer Medicine Centre and NIHR Biomedical Research Centre grants to King{\textquoteright}s Health Partners/Guy{\textquoteright}s & St Thomas{\textquoteright} NHS Foundation Trust (JS), the University of Cambridge/Cambridge University Hospitals NHS Foundation Trust (BB), University College London/UCL Hospital NHS Trust (RM), and Institute of Cancer Research/Royal Marsden Hospital (UB). We acknowledge the Immune Monitoring Core Facility team at Guy{\textquoteright}s and St Thomas{\textquoteright} NHS Foundation Trust (IS-BRC-1215-20006) for flow cytometry facilities, and the Cancer Research UK King{\textquoteright}s Health Partners Centre at King{\textquoteright}s College London (C604/A25135). The authors would like to thank the patients, their families, the clinical research teams, as well as Sharmistha Ghosh, Amy Pope and Natalie Woodman for their contribution to this study. Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = jul,
day = "25",
doi = "10.1038/s41467-023-39679-9",
language = "English",
volume = "14",
pages = "4180",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}