IgE Immunotherapy Against Cancer

Abstract

The success of antibody therapy in cancer is consistent with the ability of these molecules to activate immune responses against tumors. Experience in clinical applications, antibody design, and advancement in technology have enabled antibodies to be engineered with enhanced efficacy against cancer cells. This allows re-evaluation of current antibody approaches dominated by antibodies of the IgG class with a new light. Antibodies of the IgE class play a central role in allergic reactions and have many properties that may be advantageous for cancer therapy. IgE-based active and passive immunotherapeutic approaches have been shown to be effective in both in vitro and in vivo models of cancer, suggesting the potential use of these approaches in humans. Further studies on the anticancer efficacy and safety profile of these IgE-based approaches are warranted in preparation for translation toward clinical application.

Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy

“…Several of the Fc modifications are being validated in preclinical development and clinical trials and hence it is expected that more therapeutic antibodies with engineered Fc mutations will be approved soon. Beyond IgG, the class of choice for all the approved therapeutic antibodies used for oncologic applications, other classes of antibodies such as IgA ( 175 ) and IgE ( 176 ) are emerging as new options for cancer therapy. These new options, together with the outstanding progress in the development of antibody engineering methods to modify the V regions should lead to a profound impact in the therapy of cancer in the near future.…”

In vivo safety profile of a CSPG4-directed IgE antibody in an immunocompetent rat model

“…Using recombinant monoclonal antibodies (mAb) of the IgE class for immunotherapy of cancer is an innovative approach that has shown promising results in vitro and in vivo. [1][2][3] MAbs for the treatment of cancer are typically designed as IgGs, but use of such molecules has drawbacks, including: 1) relatively low affinity for cognate Fcγ receptors; 2) short half-life in tissues; and 3) the expression of inhibitory Fcγ receptors (FcγRIIb) on immune cells in the tumor microenvironment (TME), which may limit the effector functions and potency of IgGs to promote immune surveillance against solid tumors. 4,5 In contrast, IgE displays up to 10,000-fold higher affinities for and slow dissociation from cognate Fcε receptors on IgE effector cells often found in the TME, lacks inhibitory FcRs, is retained for longer than IgG in tissues, and can exert immune surveillance in Th2-biased environments such as the TME.…”

Antibody Isotypes for Tumor Immunotherapy

“…However, several studies addressed this issue and concluded that systemic hypersensitivity reactions caused by tumor antigen-directed IgE antibodies may not occur in a therapeutic setting. Additionally, no evidence for systemic hypersensitivity reactions due to IgE antibody therapy was seen in various in vivo models (reviewed in [51]). As a result of these in vitro and in vivo observations, an ongoing phase I clinical trial evaluates the potential of IgE antibodies in cancer immunotherapy (NCT02546921).…”