CD44 Antibody
Description
Definition and Biological Role of CD44 Antibodies
CD44 antibodies bind to epitopes on the CD44 protein, which exists in multiple isoforms generated by alternative splicing (e.g., CD44 standard [CD44s] and variant isoforms [CD44v]) . Key functions modulated by CD44 antibodies include:
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Inhibition of CD44-Hyaluronic Acid (HA) Interactions: Blocking HA binding disrupts tumor cell adhesion and metastasis .
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Immune Activation: Antibodies like 44Mab-46-mG2a activate complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) .
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Post-Translational Modification Targeting: Glycosylation states (e.g., HCELL glycoforms) influence antibody efficacy .
Antitumor Activity in Mouse Models
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Esophageal Cancer: Anti-pan-CD44 monoclonal antibodies (5-mG2a and 44Mab-46-mG2a) suppressed xenograft tumor growth by 67–88% (CHO/CD44s cells) and 27–31% (KYSE770 cells) via CDC .
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Colon Cancer: CD44v3–10-targeting antibodies reduced metastasis by 100% in murine models by blocking selectin interactions .
Mechanistic Insights
| Antibody | Target Isoform | Cytotoxicity (%) | Model |
|---|---|---|---|
| 5-mG2a | CD44s | 67 | CHO/CD44s xenograft |
| 44Mab-46-mG2a | CD44s | 88 | CHO/CD44s xenograft |
| RG7356 | CD44s | N/A | Solid tumors |
Phase I Trial of RG7356
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Design: 65 patients with CD44-expressing solid tumors received RG7356 (100–2,250 mg biweekly/weekly) .
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Results:
Therapeutic Mechanisms
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FcγR Blockade: Anti-CD44 antibodies (e.g., IM7) inhibit macrophage phagocytosis by occupying FcγR binding sites, reducing platelet clearance in immune thrombocytopenia .
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Stem Cell Targeting: CD44 antibodies deplete cancer stem cells in breast and prostate cancers by disrupting HA-mediated survival signals .
Common CD44 Antibody Clones
| Clone | Application | Species Reactivity | Vendor |
|---|---|---|---|
| #3578 | Western blot | Human | Cell Signaling |
| C44Mab-46 | Flow cytometry, IHC | Human | MDPI |
| ab157107 | IHC, Western blot | Human, Mouse | Abcam |
Key Performance Data
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Western Blot: Detects CD44 at ~81 kDa (ab157107) and ~85 kDa (AF3660) .
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Immunohistochemistry: Effective at 1:5,000 dilution in squamous cell carcinoma .
Challenges and Future Directions
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Isoform Variability: CD44v isoforms (e.g., CD44v5 in prostate cancer) correlate with better prognosis, complicating therapeutic targeting .
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Biomarker Identification: CD44s overexpression in HA-rich tumors may predict RG7356 responsiveness .
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Combination Therapies: Pairing CD44 antibodies with chemotherapy or checkpoint inhibitors enhances efficacy in preclinical models .
Product Specs
Product Science Overview
CD44 is involved in various biological processes, including:
- Lymphocyte Activation: CD44 is upregulated during T cell activation and plays a role in the inflammatory response .
- Cell Adhesion: It mediates the binding of lymphocytes to high endothelial venules, facilitating their migration back into lymphoid tissues .
- Tumor Progression: Interactions between CD44 and HER2 have been linked to increased ovarian carcinoma cell growth .
CD44 is expressed in a wide range of tissues, including:
- Immune Cells: High levels are found on the surface of T cells, B cells, and macrophages .
- Epithelial Cells: It is present in various epithelial tissues, contributing to cell adhesion and migration .
- Cancer Cells: Elevated levels of CD44 are often observed in cancerous tissues, where it is associated with tumor progression and metastasis .
The primary functions of CD44 include:
- Cell Migration: CD44 interacts with the actin cytoskeleton through its association with ezrin, radixin, and moesin (ERM) proteins, facilitating cell movement .
- Signal Transduction: It participates in signaling pathways that regulate cell proliferation, survival, and differentiation .
- Matrix Degradation: CD44 contributes to the degradation of the ECM, promoting tissue remodeling and repair .
CD44 mediates its effects through several mechanisms:
- Ligand Binding: It binds to HA and other ECM components, initiating downstream signaling pathways .
- Protein Interactions: CD44 interacts with various intracellular proteins, linking the ECM to the cytoskeleton and influencing cell behavior .
- Phosphorylation: The phosphorylation state of CD44 regulates its interactions with other proteins and its role in cell migration .
The expression and activity of CD44 are regulated by:
- Alternative Splicing: Different splice variants of CD44 are produced in response to various physiological and pathological conditions .
- Post-Translational Modifications: Glycosylation, phosphorylation, and other modifications influence the function and localization of CD44 .
- Transcriptional Regulation: The expression of CD44 is controlled by various transcription factors and signaling pathways .
Mouse anti-human CD44 antibodies are widely used in research to study the expression and function of CD44 in human tissues. These antibodies are developed by immunizing mice with human CD44 protein, and they are used in various applications, including:
