Therapeutic IgE Antibodies: Harnessing a Macrophage-Mediated Immune Surveillance Mechanism against Cancer

Cancer Research
Sophia N KaragiannisJ F Spicer

Abstract

IgG monoclonal antibodies have made significant contributions to cancer therapy, but suffer from several limitations that restrict their effectiveness in unleashing host immune system components against tumors. The development of monoclonal antibodies of an alternative class, namely IgE, may offer enhanced immune surveillance and superior effector cell potency against cancer cells. In our recent article, we elaborate our proof-of-concept studies of a mouse/human chimeric IgE antibody (MOv18 IgE), which is specific for the cancer-associated antigen folate receptor alpha. We demonstrate superior antitumor efficacy for IgE compared with an otherwise identical IgG in a syngeneic immunocompetent animal, and we identify TNFα/MCP-1 signaling as an IgE-mediated mechanism of monocyte and macrophage activation and recruitment to tumors. These findings draw parallels with powerful macrophage-activating functions employed by IgE against parasites, rather than allergic IgE mechanisms. The potential clinical application of IgE-derived drugs in clinical oncology is clear if the antitumor activity of MOv18 IgE in these preclinical experiments can be replicated in patients. In particular, different IgE antibodies with specificity for many other...Continue Reading

References

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Citations

Sep 19, 2017·Allergy·E Jensen-JarolimS N Karagiannis
Apr 30, 2020·Current Opinion in Allergy and Clinical Immunology·Judit Fazekas-SingerErika Jensen-Jarolim
Mar 6, 2019·Frontiers in Immunology·Jesse D PlotkinChristopher L Kepley
Apr 30, 2019·Frontiers in Immunology·Arianne M BrandsmaToine Ten Broeke
Sep 30, 2017·Frontiers in Immunology·Kristina M IlievaSophia N Karagiannis
Mar 15, 2019·Journal of Experimental & Clinical Cancer Research : CR·Barbara FrigerioMariangela Figini
Sep 24, 2019·Antibodies·Brian J SuttonSophia N Karagiannis
Oct 22, 2019·Frontiers in Bioengineering and Biotechnology·Laura Montero-MoralesHerta Steinkellner
Nov 19, 2020·Cancers·Mano NakamuraSophia N Karagiannis

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