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Although antibodies in clinical cancer therapy are generally of the IgG class, antibodies of the IgE class have attractive properties as cancer therapeutics, such as their high affinity for Fc receptors (Fc\u03b5Rs), the low serum levels of endogenous IgE allowing for less competition for FcR occupancy, and the lack of inhibitory FcRs. Importantly, the Fc\u03b5Rs are expressed on immune cells that elicit antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and\/or antigen presentation such as mast cells, eosinophils, macrophages, and dendritic cells. We now report the development of a fully human IgE targeting human CD38 as a potential MM therapy. We targeted CD38 given its high and uniform expression on MM cells. The novel anti-CD38 IgE, expressed in mammalian cells, is properly assembled and secreted, exhibits the correct molecular weight, binds antigen and the high affinity Fc\u03b5RI, and induces degranulation of Fc\u03b5RI expressing cells in vitro and also in vivo in transgenic BALB\/c mice expressing human Fc\u03b5RI\u03b1. Moreover, the anti-CD38 IgE induces ADCC and ADCP mediated by monocytes\/macrophages against human MM cells (MM.1S). Importantly, the anti-CD38 IgE also prolongs survival in a preclinical disseminated xenograft mouse model using SCID-Beige mice and human MM.1S cells when administered with human peripheral blood mononuclear cells (PBMCs) as a source of monocyte effector cells. Our results suggest that anti-CD38 IgE may be effective in humans bearing MM and other malignancies expressing CD38.<\/jats:p>","DOI":"10.3390\/cancers15184533","type":"journal-article","created":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T05:08:21Z","timestamp":1694581701000},"page":"4533","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A Fully Human IgE Specific for CD38 as a Potential Therapy for Multiple Myeloma"],"prefix":"10.3390","volume":"15","author":[{"given":"Pierre V.","family":"Candelaria","sequence":"first","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Nava","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8277-9702","authenticated-orcid":false,"given":"Tracy R.","family":"Daniels-Wells","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel L.","family":"Penichet","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA"},{"name":"Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA"},{"name":"UCLA AIDS Institute, Los Angeles, CA 90095, USA"},{"name":"UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA"},{"name":"The Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1159\/000520312","article-title":"Multiple Myeloma: Molecular Pathogenesis and Disease Evolution","volume":"44","author":"Heider","year":"2021","journal-title":"Oncol. 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