Epratuzumab, a CD22-targeting recombinant humanized antibody with a different mode of action from rituximab
Abstract
Epratuzumab is a humanized anti-CD22 monoclonal antibody currently in clinical trials for treatment of non-Hodgkin lymphoma (NHL) and certain autoimmune diseases. Here we report the results of investigations of epratuzumab's mode of action in comparison to and in combination with the anti-CD20 mAb, rituximab. In vitro cell growth inhibition, induction of apoptosis, and the ability of the mAbs to mediate complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) were evaluated. We also investigated the potential activity of epratuzumab in the regulation of B-cell antigen receptor (BCR) activation. Epratuzumab and rituximab displayed very distinct modes of action; epratuzumab acts as an immunomodulatory agent, while rituximab is an acutely cytotoxic therapeutic antibody. Epratuzumab has distinct effects on cell growth from rituximab. For example, rituximab+anti-human IgG Fcgamma yielded marked inhibition of proliferation in human NHL cell lines, while epratuzumab had little or no effect in this assay. However, when cells were immobilized and stimulated with anti-IgM, epratuzumab, but not rituximab, caused a significant antiproliferative effect. Unlike rituximab, no CDC could be detected, and ADCC was modest but significant with epratuzumab. Importantly, combining rituximab and epratuzumab did not decrease rituximab's ability to induce apoptosis, CDC, and ADCC. In fact, the combination is more effective than rituximab alone in inhibiting proliferation of Daudi Burkitt lymphoma cells in the presence of second antibody, and at least equally effective to rituximab in the absence of crosslinking. These observations suggest that it may be possible to enhance clinical efficacy by combination therapy comprised of anti-CD20 and anti-CD22 mAbs.
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The CD22-specific agent epratuzumab stimulates immunity through ADCC, ADCP, or complement-dependent cytotoxicity.
“the CD22-specific drug epratuzumab”
From Immunomodulation by targeted anticancer agents (2021) · cites this paper as Carnahan et al., 2007
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Immunomodulation by targeted anticancer agents
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“Unlike Rituximab, which depletes circulating B cells, Emab does not induce complement-dependent cytotoxicity or Abdependent cellular cytotoxicity (115).”
Background
- Authors
- Carnahan, J., Stein, R., Qu, Z., Hess, K., Cesano, A., Hansen, H. J., & Goldenberg, D. M.
- Affiliations
- Amgen (United States) (US)
- Center for Molecular Medicine and Immunology (US)
- Immunomedics (United States) (US)
- Corresponding author
- Stein, Rhona
- Venue
- Molecular Immunology
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 44
- Issue
- 6
- Pages
- 1331-1341
- ISSN
- 0161-5890 (ISSN-L)
- OpenAlex
- W2054409932
- Cited by
- 175
- References
- 48
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 6 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 11 · 2014: 10 · 2013: 13 · 2012: 15
- FWCI
- 12.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centers for Disease Control and Prevention
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Keywords
- epratuzumab, rituximab, anti-CD22 monoclonal antibody, anti-CD20 monoclonal antibody, non-Hodgkin lymphoma, B-cell lymphoma, B cell receptor signaling, apoptosis, complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, immunomodulation, combination therapy, Daudi cells, Burkitt lymphoma
- MeSH terms
- Rituximab, Antibodies, Monoclonal, Antigens, Neoplasm, Antineoplastic Agents, Burkitt Lymphoma, Humans, Recombinant Proteins, Apoptosis, Cell Line, Tumor, Sialic Acid Binding Ig-like Lectin 2, Antibodies, Monoclonal, Murine-Derived, Antibodies, Monoclonal, Humanized
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