IgE Antibodies against Cancer: Efficacy and Safety

Chauhan, Jitesh; McCraw, Alex J.; Nakamura, Mano; Osborn, Gabriel; Sow, Heng Sheng; Cox, Vivienne F.; Stavraka, Chara; Josephs, Debra H.; Spicer, James; Karagiannis, Sophia N.; Bax, Heather J.

doi:10.3390/antib9040055

Cited by 20 publications

(18 citation statements)

References 137 publications

(261 reference statements)

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“…If these events occur in the blood, they can potentiate systemic anaphylaxis. Inspired by the emerging studies in the field of allergy, the BAT was developed as one of the experimental assays to be applied alongside several clinical assays for the prediction and monitoring of the potential for anaphylaxis with IgE immunotherapy for the first-in-class IgE in oncology [97,115]. We show in Figure 4A the proposed schema of the mechanism of action of three positive controls (anti-FcεRI, fMLP, and anti-IgE) in the upregulation of cell surface CD63 through the fusion of intracellular vesicles with the cell surface membrane in the accompanying representative flow plots of the upregulation of basophil activation marker CD63 in CCR3 + basophils (Figure 4B).…”

Section: Basophil Activation Evaluated In the Bat As A Tool To Predict Propensity For Type 1 Hypersensitivity To Emerging Ige Immunotheramentioning

confidence: 99%

Clinical and Translational Significance of Basophils in Patients with Cancer

Chauhan

Stavraka

Grandits

et al. 2022

Cells

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Despite comprising a very small proportion of circulating blood leukocytes, basophils are potent immune effector cells. The high-affinity receptor for IgE (FcɛRI) is expressed on the basophil cell surface and powerful inflammatory mediators such as histamine, granzyme B, and cytokines are stored in dense cytoplasmic granules, ready to be secreted in response to a range of immune stimuli. Basophils play key roles in eliciting potent effector functions in allergic diseases and type 1 hypersensitivity. Beyond allergies, basophils can be recruited to tissues in chronic and autoimmune inflammation, and in response to parasitic, bacterial, and viral infections. While their activation states and functions can be influenced by Th2-biased inflammatory signals, which are also known features of several tumor types, basophils have received little attention in cancer. Here, we discuss the presence and functional significance of basophils in the circulation of cancer patients and in the tumor microenvironment (TME). Interrogating publicly available datasets, we conduct gene expression analyses to explore basophil signatures and associations with clinical outcomes in several cancers. Furthermore, we assess how basophils can be harnessed to predict hypersensitivity to cancer treatments and to monitor the desensitization of patients to oncology drugs, using assays such as the basophil activation test (BAT).

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Section: Basophil Activation Evaluated In the Bat As A Tool To Predict Propensity For Type 1 Hypersensitivity To Emerging Ige Immunotheramentioning

confidence: 99%

Clinical and Translational Significance of Basophils in Patients with Cancer

Chauhan

Stavraka

Grandits

et al. 2022

Cells

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“…The mechanisms underlying the anti-tumor effects of therapeutic IgE’s are mostly attributed to monocyte and macrophage infiltration and subsequent IgE-mediated activation of these cells around tumors ( 56 , 65 , 129 , 130 ). This hypothesized mechanism seems counter-intuitive to current evidence that demonstrates tumor-infiltrating myeloid cells promote, rather than inhibit-cancer progression ( 10 ).…”

Section: Could Mcs Mediate the Efficacy Of Anti-tumor Ige’s And In Ig...mentioning

confidence: 99%

Harnessing the Anti-Tumor Mediators in Mast Cells as a New Strategy for Adoptive Cell Transfer for Cancer

et al. 2022

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The emergence of cancer immunotherapies utilizing adoptive cell transfer (ACT) continues to be one of the most promising strategies for cancer treatment. Mast cells (MCs) which occur throughout vascularized tissues, are most commonly associated with Type I hypersensitivity, bind immunoglobin E (IgE) with high affinity, produce anti-cancer mediators such as tumor necrosis factor alpha (TNF-α) and granulocyte macrophage colony-stimulating factor (GM-CSF), and generally populate the tumor microenvironments. Yet, the role of MCs in cancer pathologies remains controversial with evidence for both anti-tumor and pro-tumor effects. Here, we review the studies examining the role of MCs in multiple forms of cancer, provide an alternative, MC-based hypothesis underlying the mechanism of therapeutic tumor IgE efficacy in clinical trials, and propose a novel strategy for using tumor-targeted, IgE-sensitized MCs as a platform for developing new cellular cancer immunotherapies. This autologous MC cancer immunotherapy could have several advantages over current cell-based cancer immunotherapies and provide new mechanistic strategies for cancer therapeutics alone or in combination with current approaches.

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“…There are more folate receptor alpha in many cancer cell types compared to the normal cells, and IgE type chimeric antibody (MOv18 IgE) phase 1 (ClinicalTrials.gov NCT02546921) trials have been carried out for this receptor [29]. Recently, numerous chimeric IgE studies have been carried out for use in cancer treatment [30].…”

Section: Discussionmentioning

confidence: 99%

Is There a Clinical Significance of Very Low Serum Immunoglobulin E Level?

Asilsoy

Uzuner

et al. 2021

J Clin Immunol

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Purpose: It has been well known that high serum immunoglobulin (Ig) E levels are associated with allergies, parasitic infections and some immune de ciencies; however, the potential effects and clinical implications of low IgE level on the human immune system are not well known. To determine the disorders accompanying very low IgE levels in children and adults.Methods: The patients whose IgE levels were determined between January 2015 and September 2020 were analyzed, and the ones with an IgE level <2.5 IU/mL were included in the study. Demographic data, immunoglobulin levels, auto-antibody results, and the diagnoses of the patients were noted from the electronic recording system of the hospital. Result: The IgE levels were measured in 34,809 patients (21,875 children, 12,934 adults), and 180 patients had IgE levels <2.5 IU/mL. Eighty patients were children (0.37%), 100 were adults (0.77%). There was a malignant disease in 45 (11 of them children) (25%), autoimmune diseases in 30 (4 of them children) (16.7%) and immunode ciency in 19 (16 of them children) (10.6%) of the patients. The most common reasons were other disases, immunode ciency and malignancy in children; and malignancy, autoimmune disorders and other diseases in the adults, in rank order. The IgE level did not show any correlation with the levels of other immunoglobulins. Conclusion: Although rare, a low IgE level has been shown to accompany malignancies, autoimmune disorders and immune de ciencies. Patients with very low IgE levels should be carefully monitored for systemic disorders.

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IgE Antibodies against Cancer: Efficacy and Safety

Cited by 20 publications

References 137 publications

Clinical and Translational Significance of Basophils in Patients with Cancer

Clinical and Translational Significance of Basophils in Patients with Cancer

Harnessing the Anti-Tumor Mediators in Mast Cells as a New Strategy for Adoptive Cell Transfer for Cancer

Is There a Clinical Significance of Very Low Serum Immunoglobulin E Level?

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