Currently, all antibodies approved for the treatment of cancer belong to the IgG class. In this context, the emergence of IgE antibodies offers exciting prospects. Compared to IgG, IgE has a stronger immune response and may have a more targeted and effective effect on tumor cells. This could provide a more effective mechanism to destroy cancer cells. Recently, Cancer Research UK facilitated a pivotal clinical trial to test a novel class of IgE antibodies as a potential solution to cancer.
Introduction to MOv18 IgE
MOv18 IgE is an antibody developed by researchers at King's College London that has shown promising efficacy in the treatment of cancer, particularly in patients for whom existing therapies have failed. The MOv18 antibody targets the human folate receptor-alpha (FRα), which is overexpressed in tumors such as ovarian, breast, and lung cancers but remains at low levels in normal tissues. Gould et al. constructed a mouse/human chimeric MOv18 IgE and IgG1 antibody against the mouse/human chimeric MOv18 IgE and IgG1 antibodies against the ovarian cancer antigen FRα. SCID mice were subjected to subcutaneous attack with human IGROV1 ovarian cancer cells, implanted with human PBMCs and treated with either MOv18 IgE or IgG1. Although tumor growth was initially limited in IgG1-treated animals, by day 35 after attack, tumor size was comparable to controls. In contrast, at day 35, tumor growth in mice treated with PBMC and MOv18 IgE was restricted by up to 72%.1
Fig 1. Mechanism of cytotoxicity mediated by MOv18 IgE.2
Encouraging Results from Phase I Clinical Trial of MOv18 IgE
The primary objective of the Phase I dose-escalation trial was to explore the safety and tolerability of MOv18 IgE in patients with tumors expressing the relevant FRα. The trial combined skin prick and basophil activation test (BAT) to select patients with the lowest risk of allergic toxicity. The trial demonstrated good tolerance of MOv18 IgE in the majority of patients. The antibody even successfully shrunk tumors in ovarian cancer patients who did not respond to standard treatment, paving the way for a new class of drugs to treat chemotherapy-resistant cancers.
The Future of MOv18 IgE
The first IgE antibody trial is of great scientific importance because it stimulates a unique and powerful immune response. To ensure the safety of MOv18 IgE in patients, researchers plan to continue its clinical development beyond this successful trial. The ultimate goal is to target cancer cells with similar efficiency, introducing a new therapeutic alternative for patients. Key contributors to the study also expressed positive views on the IgE antibody. They emphasized the potential of IgE as a revolutionary antibody therapy and how the trial builds on earlier IgE research. Although this area of research is still in its early stages, continued research into the capabilities of IgE antibodies could awaken the body's immune response against different cancers.
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- Gould, Hannah J., et al. "Comparison of IgE and IgG antibody‐dependent cytotoxicity in vitro and in a SCID mouse xenograft model of ovarian carcinoma." European journal of immunology 29.11 (1999): 3527-3537.
- Spicer, James, et al. "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 (2023): 4180.
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