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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-39679-9 |
| _version_ | 1797769412841832448 |
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| author | James Spicer Bristi Basu Ana Montes Udai Banerji Rebecca Kristeleit Rowan Miller Gareth J. Veal Christopher J. Corrigan Stephen J. Till Mariangela Figini Silvana Canevari Claire Barton Paul Jones Sarah Mellor Simon Carroll Chris Selkirk George Nintos Vineet Kwatra Ionut-Gabriel Funingana Gary Doherty Hannah J. Gould Giulia Pellizzari Mano Nakamura Kristina M. Ilieva Atousa Khiabany Chara Stavraka Jitesh Chauhan Cheryl Gillett Sarah Pinder Heather J. Bax Debra H. Josephs Sophia N. Karagiannis |
| author_facet | James Spicer Bristi Basu Ana Montes Udai Banerji Rebecca Kristeleit Rowan Miller Gareth J. Veal Christopher J. Corrigan Stephen J. Till Mariangela Figini Silvana Canevari Claire Barton Paul Jones Sarah Mellor Simon Carroll Chris Selkirk George Nintos Vineet Kwatra Ionut-Gabriel Funingana Gary Doherty Hannah J. Gould Giulia Pellizzari Mano Nakamura Kristina M. Ilieva Atousa Khiabany Chara Stavraka Jitesh Chauhan Cheryl Gillett Sarah Pinder Heather J. Bax Debra H. Josephs Sophia N. Karagiannis |
| author_sort | James Spicer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T21:07:41Z |
| format | Article |
| id | doaj.art-10c6fe5134614037a52da348794ee12d |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-12T21:07:41Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-10c6fe5134614037a52da348794ee12d2023-07-30T11:19:54ZengNature PortfolioNature Communications2041-17232023-07-0114111110.1038/s41467-023-39679-9Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trialJames Spicer0Bristi Basu1Ana Montes2Udai Banerji3Rebecca Kristeleit4Rowan Miller5Gareth J. Veal6Christopher J. Corrigan7Stephen J. Till8Mariangela Figini9Silvana Canevari10Claire Barton11Paul Jones12Sarah Mellor13Simon Carroll14Chris Selkirk15George Nintos16Vineet Kwatra17Ionut-Gabriel Funingana18Gary Doherty19Hannah J. Gould20Giulia Pellizzari21Mano Nakamura22Kristina M. Ilieva23Atousa Khiabany24Chara Stavraka25Jitesh Chauhan26Cheryl Gillett27Sarah Pinder28Heather J. Bax29Debra H. Josephs30Sophia N. Karagiannis31School of Cancer and Pharmaceutical Sciences, King’s College LondonCambridge University Hospitals NHS Foundation Trust, and Cancer Research UK Cambridge Centre, University of CambridgeCancer Centre, Guy’s and St Thomas’ NHS Foundation TrustInstitute of Cancer Research and Royal Marsden Hospital NHS Foundation TrustCancer Centre, Guy’s and St Thomas’ NHS Foundation TrustUniversity College LondonNewcastle University Centre for CancerKing’s Centre for Lung Health, School of Immunology and Microbial Sciences, King’s College LondonKing’s Centre for Lung Health, School of Immunology and Microbial Sciences, King’s College LondonANP2, Department of Advanced Diagnostics, Fondazione IRCCS, Istituto Nazionale dei TumoriFondazione IRCCS, Istituto Nazionale dei TumoriCentre for Drug Development, Cancer Research UKCentre for Drug Development, Cancer Research UKCentre for Drug Development, Cancer Research UKCentre for Drug Development, Cancer Research UKCentre for Drug Development, Cancer Research UKCancer Centre, Guy’s and St Thomas’ NHS Foundation TrustCancer Centre, Guy’s and St Thomas’ NHS Foundation TrustCambridge University Hospitals NHS Foundation Trust, and Cancer Research UK Cambridge Centre, University of CambridgeCambridge University Hospitals NHS Foundation Trust, and Cancer Research UK Cambridge Centre, University of CambridgeKing’s Centre for Lung Health, School of Immunology and Microbial Sciences, King’s College LondonSt. John’s Institute of Dermatology, School of Basic and Medical Biosciences, King’s College LondonSt. John’s Institute of Dermatology, School of Basic and Medical Biosciences, King’s College LondonSt. John’s Institute of Dermatology, School of Basic and Medical Biosciences, King’s College LondonSt. John’s Institute of Dermatology, School of Basic and Medical Biosciences, King’s College LondonSchool of Cancer and Pharmaceutical Sciences, King’s College LondonSt. John’s Institute of Dermatology, School of Basic and Medical Biosciences, King’s College LondonSchool of Cancer and Pharmaceutical Sciences, King’s College LondonSchool of Cancer and Pharmaceutical Sciences, King’s College LondonSchool of Cancer and Pharmaceutical Sciences, King’s College LondonSchool of Cancer and Pharmaceutical Sciences, King’s College LondonSt. John’s Institute of Dermatology, School of Basic and Medical Biosciences, King’s College LondonAbstract 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.https://doi.org/10.1038/s41467-023-39679-9 |
| spellingShingle | James Spicer Bristi Basu Ana Montes Udai Banerji Rebecca Kristeleit Rowan Miller Gareth J. Veal Christopher J. Corrigan Stephen J. Till Mariangela Figini Silvana Canevari Claire Barton Paul Jones Sarah Mellor Simon Carroll Chris Selkirk George Nintos Vineet Kwatra Ionut-Gabriel Funingana Gary Doherty Hannah J. Gould Giulia Pellizzari Mano Nakamura Kristina M. Ilieva Atousa Khiabany Chara Stavraka Jitesh Chauhan Cheryl Gillett Sarah Pinder Heather J. Bax Debra H. Josephs Sophia N. Karagiannis 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 |
| 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 |
| title_full | Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trial |
| title_fullStr | Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trial |
| title_full_unstemmed | Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trial |
| title_short | Safety and anti-tumour activity of the IgE antibody MOv18 in patients with advanced solid tumours expressing folate receptor-alpha: a phase I trial |
| title_sort | safety and anti tumour activity of the ige antibody mov18 in patients with advanced solid tumours expressing folate receptor alpha a phase i trial |
| url | https://doi.org/10.1038/s41467-023-39679-9 |
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