FLA21 Antibody
Description
Clarification of Terminology
The term "FLA21" does not correspond to a recognized antibody or protein in current immunological literature. Potential misinterpretations include:
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Flightless Homolog (FLII): A protein targeted by monoclonal antibodies (e.g., clone AB01/1C12), involved in actin remodeling and implicated in inflammatory diseases .
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Flagellin Antibodies: Detected in Crohn’s disease patients, targeting microbial antigens like A4-Fla2 and Fla-X .
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IL-21 Antibodies: Therapeutic agents (e.g., AMG 256) targeting IL-21 for autoimmune or inflammatory conditions .
Antibody Structure
Monoclonal antibodies (mAbs) typically consist of:
IgG subclasses (e.g., IgG1, IgG2, IgG3, IgG4) vary in Fc-mediated functions and half-life (Table 1) .
Table 1: IgG Isotype Characteristics
| Property | IgG1 | IgG2 | IgG3 | IgG4 |
|---|---|---|---|---|
| Molecular Weight (kDa) | 150 | 150 | 170 | 150 |
| Hinge Disulfide Bonds | 2 | 4 | 11 | 2 |
| Half-life (days) | 14–21 | 14–21 | 7 | 14–21 |
| Serum Abundance (%) | 60 | 32 | 4 | 4 |
Case Study: Anti-IL-21 Antibodies
AMG 256, a dual-targeting antibody, combines anti-IL-21 and anti-PD-1 domains. Key findings from preclinical and clinical studies include:
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Immunogenicity: High ADA (anti-drug antibody) response in cynomolgus monkeys, primarily targeting the anti-PD-1 domain .
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Cross-reactivity: Detected anti-IL-21 antibodies in 2/4 FIH trial patients, with neutralizing potential .
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Safety: Hypersensitivity events linked to IgE ADAs in non-human primates .
Table 2: AMG 256 Immunogenicity Profile
| Parameter | Cynomolgus Monkeys | FIH Trial Patients |
|---|---|---|
| ADA Prevalence | 100% (AMG 256) | 50% (Cohorts 1–2) |
| IgE ADAs Detected | 75% | 2/4 |
| Neutralizing Ab | N/A | 2/4 |
Flagellin Antibodies in Crohn’s Disease
Anti-A4-Fla2 and Fla-X antibodies correlate with disease phenotypes:
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Association:
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Multiplex Serology: Patients with ≥3 microbial antibodies showed higher rates of complications .
Research Challenges and Innovations
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Antibody Validation: ELISA positivity does not always predict utility in immunohistochemistry or Western blotting .
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Glycoengineering: Modifying Fc glycans (e.g., afucosylation) enhances ADCC activity for cancer therapies .
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Benchmarks: FLAb framework evaluates antibody fitness for expression, thermostability, and immunogenicity .
