CHS1B Antibody
Description
Structure and Mechanism of Action
CHS-114 is constructed as a humanized IgG1 antibody, comprising two heavy chains and two light chains arranged in a Y-shaped structure. The Fab fragments at the tips of the Y-shape bind to CCR8 with high affinity, while the Fc region interacts with immune effector cells . The afucosylation of the Fc region enhances antibody-dependent cellular cytotoxicity (ADCC) by increasing binding to Fcγ receptors on immune cells .
Phase 1 Trial Overview
| Parameter | Details |
|---|---|
| Dosing | 5–700 mg administered every 3 weeks |
| Patient Cohort | Heavily pretreated solid tumor pts |
| Primary Objectives | Safety, tolerability, PK/PD |
| Secondary Objectives | Antitumor activity, immune biomarkers |
Mechanism of Action
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Target Engagement: High-affinity binding to CCR8 on Tregs.
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ADCC: Afucosylation enhances Fc-mediated immune cell activation.
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Immune Modulation: Reduces immune suppression, enabling cytotoxic T-cell activity .
Future Directions
The Phase 1 trial is ongoing, with dose escalation continuing beyond 700 mg. Combination studies with toripalimab (anti-PD-1 mAb) are planned for head and neck squamous cell carcinoma (HNSCC) patients, using a 3+3 design . Exploratory analyses include tumor biopsy-based biomarker studies to correlate CCR8 expression with clinical outcomes.
References
Product Specs
**Constituents:** 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
STRING: 4113.PGSC0003DMT400076178
UniGene: Stu.186
