CCR4-2 Antibody
Description
Structure and Function of CCR4
CCR4 is a seven-transmembrane receptor encoded by the CCR4 gene on human chromosome 3p24. It binds ligands CCL17 (TARC) and CCL22 (MDC), facilitating chemotaxis of T cells, particularly Th2, Th17, Tregs, and skin-homing memory T cells . Its roles include:
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Immune Regulation: Mediates recruitment of Tregs to tumor microenvironments (TME), suppressing antitumor immunity .
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Pathological Roles: Overexpressed in cutaneous T-cell lymphoma (CTCL), adult T-cell leukemia/lymphoma (ATLL), and solid tumors .
Mogamulizumab
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Type: Humanized IgG1 monoclonal antibody (mAb) with glyco-engineered Fc for enhanced ADCC .
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Mechanism: Depletes CCR4+ malignant T cells and Tregs via antibody-dependent cellular cytotoxicity (ADCC) .
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Clinical Use:
mAb1567 and Humanized Variants
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Target: Binds CCR4’s N-terminal and extracellular domains, inhibiting CCL17/22-mediated chemotaxis .
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Optimization: Affinity-matured variants (e.g., mAb2-3) enhance ADCC and CDC (complement-dependent cytotoxicity) .
Research Antibodies
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Clone AF5207 (R&D Systems): Sheep polyclonal antibody for Western blotting, detects ~42 kDa CCR4 in mouse models .
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Clone 9E10J (PLOS ONE): Fully human scFv with sub-nM affinity, blocks CCL17/22-induced migration (IC₅₀: 0.1–3.7 nM) .
Treg Inhibition in Cancer
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CCR4 blockade reduces Treg infiltration into tumors, synergizing with checkpoint inhibitors (CPIs) like anti-PD-1 .
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In Pan02 (high CCL17/22) and CT26 (low CCL17/22) mouse models, CCR4 antagonist CCR4-351 improved CPI efficacy by 40–60% .
Ligand Binding and Signaling
| Antibody | Target Epitope | Ligand Inhibition | Functional Impact |
|---|---|---|---|
| Mogamulizumab | Extracellular domain | CCL17 > CCL22 | Depletes CCR4+ Tregs and tumor cells |
| mAb2-3 | N-terminal + ECLs | CCL17 = CCL22 | Blocks chemotaxis, enhances ADCC |
| 9E10J | Ligand-binding pocket | CCL17 > CCL22 | Inhibits migration (IC₅₀: 0.1 nM) |
Emerging Strategies and Challenges
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
- AtCCR4a and AtCCR4b are localized to cytoplasmic foci known as processing bodies (P-bodies). They are involved in sucrose and starch metabolism and have been shown to influence the poly(A) length of the Granule-bound starch synthase 1 (GBSS1) transcript. [AtCCR4b] PMID: 25630334
