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The First Anti-Tumour Chimeric IgE Monoclonal Antibody

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IgE antibodies are well known for their role in allergic diseases and for contributions to antiparasitic immune responses. However, increasing evidence indicates significant bioactivity for IgE in tumor immunosurveillance. Properties of this antibody class that mediates powerful effector functions may be redirected for the treatment of solid tumors. This has led to the rise of a new class of therapeutic antibodies to complement the armamentarium of approved tumor-targeting antibodies, which are all IgG class. Therefore, the anti-tumor activity of IgE was highlighted by the successes of the first-in-class IgE cancer therapeutic focus to Folate Receptor alpha (FRα). As an advanced biotech company, Creative Biolabs is continuously concerned about the progress of the first anti-tumor chimeric monoclonal IgE and we are glad to share our idea about the application of IgE.

Introduction of IgE

IgE was the last of the five classes of human antibodies to be discovered and is commonly associated with the various manifestations of allergic disease. The most significant difference of IgE molecule from IgG is the additional heavy chain constant domain and the absence of a hinge region in the ε-chain. While both FcεRI and CD23 are recognized as IgE-receptors, IgE cannot bind to both receptors simultaneously due to allosteric effects.

Overall structure and glycosylation. Fig.1 Overall structure and glycosylation. (Sutton, 2019)

IgE-Mediated Functions Against Cancer

It is obvious that IgE is a powerful activator of the immune system by virtue of the Fc receptor interactions. Moreover, several unique attributes of IgE make it suitable for the immunotherapy of solid tumors such as high affinity for receptors, long tissue residency and immune surveillance, the ability to potentiate strong effector functions in low concentration, and a lack of inhibitory Fc receptors. Meanwhile, epidemiological reports also support a functional role for IgE as a passive or active component in anti-tumour responses.

IgE therapy-mediated cellular immune surveillance against cancer. Fig.2 IgE therapy-mediated cellular immune surveillance against cancer. (McCraw, 2021)

Introduction of the First Anti-Tumour IgE Anribody to Reach Clinical Testing

An IgE antibody that has progressed to clinical testing as a mouse/human chimeric monoclonal IgE antibody that recognizes the tumour-associated antigen FRα, which is highly expressed in most ovarian carcinomas while has restricted expression in normal tissues. This IgE therapeutic antibody could mediate cytotoxicity and phagocytosis by activating known IgE effector cells and realizing tumour cell killing. With the effective result in the in vivo and in vitro studies, IgE therapeutic antibody was promoted in clinical testing in 2019. Although the potential risk of anaphylaxis has been recognized, initial results support the safety and anti-tumour activity of anticancer IgE therapy.

While the IgG represents the majority of currently approved therapeutic mAbs, the appearance of the first anti-tumour chimeric monoclonal IgE provides a novel approach in cancer research. Although faced with some difficulties including GMP process development and unknown safety risk, IgE therapy is still promising as a new generation of anti-tumor technology. If you are interested in the research of anti-tumour chimeric monoclonal IgE, or for more details in the research of the therapeutic molecular field, please feel free to contact us.

References

  1. Sutton, B. J.; et al. IgE antibodies: from structure to function and clinical translation. Antibodies. 2019, 8(1), 19.
  2. McCraw, A. J.; et al. Insights from IgE immune surveillance in allergy and cancer for anti-tumour IgE treatments. Cancers. 2021, 13(17), 4460.

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