CRF6 Antibody
Description
Introduction to CCR6 and Its Antibodies
CCR6 is a G protein-coupled receptor (GPCR) that binds exclusively to its ligand CCL20, playing critical roles in immune cell migration, inflammation, and autoimmune diseases . Antibodies targeting CCR6 are engineered to modulate this interaction, offering therapeutic potential in conditions like cancer, psoriasis, and rheumatoid arthritis .
Table 1: Binding Kinetics of C6Mab-13 to CCR6 Mutants
| Peptide Mutation | Association Rate (kₐ) | Dissociation Rate (kₑ) | KD (M) |
|---|---|---|---|
| Wild-Type | 6.84 × 10³ | 3.77 × 10⁻³ | 5.52 × 10⁻⁷ |
| F8A | 1.43 × 10³ | 1.23 × 10⁻² | 8.55 × 10⁻⁶ |
| D11A | ND | ND | ND |
ND: Not determined due to lack of binding.
Mechanisms of Action
CCR6 antibodies exert effects through:
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Receptor Blockade: Inhibiting CCL20 binding, thereby disrupting chemotaxis of CCR6-expressing cells (e.g., Th17 and Treg cells) .
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Effector Functions: Fc-mediated mechanisms like antibody-dependent cellular cytotoxicity (ADCC) or phagocytosis (ADCP) .
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Diagnostic Utility: Flow cytometry applications (e.g., BD Horizon™ BUV661 anti-human CCR6) enable immune cell profiling .
4.1. Autoimmune Diseases
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Psoriasis: CCR6/CCL20 axis drives Th17 cell infiltration into skin lesions .
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Rheumatoid Arthritis: Preclinical models show reduced joint inflammation with CCR6 blockade .
4.2. Cancer
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Tumor Microregulation: Depletion of CCR6⁺ Treg cells enhances antitumor immunity .
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CAR-T Cell Therapy: CCR6-targeted CAR-T cells are under investigation for solid tumors .
5.1. Epitope Mapping
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C6Mab-13 loses binding to D11A mutants, confirming Asp11 as critical for antigen recognition .
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Alanine scanning identified secondary residues (Phe8, Thr10, Tyr13) contributing to affinity .
5.2. Preclinical Efficacy
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Mouse Models: C6Mab-13 demonstrated high affinity (KD = 2.8 × 10⁻⁹ M) in flow cytometry, supporting its use in vivo .
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Inflammatory Bowel Disease: Anti-CCR6 antibodies reduced leukocyte recruitment in murine colitis models .
Challenges and Future Directions
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
- Research indicates that CRF6 functions as a negative regulator during oxidative stress, controlling the cytokinin-associated module of CRF6-dependent genes. This finding establishes a novel link between cytokinin and the oxidative stress response. PMID: 27550996
- CRFs represent a crucial cross-talk component that fine-tunes auxin transport capacity downstream of cytokinin signaling. This regulation influences plant development through transcriptional control of PIN-FORMED auxin transporters. PMID: 26541513
- CRF6 plays a regulatory role in negatively controlling developmental senescence, suggesting a similar function in response to stress. PMID: 23539244
