FATA2 Antibody
Description
Antibody Structure and Function
Antibodies are Y-shaped glycoproteins comprising two heavy chains and two light chains, with distinct regions for antigen binding (Fab fragments) and effector functions (Fc region) . Engineered variants like F(ab) and F(ab')₂ fragments enhance specificity by eliminating non-specific Fc-mediated interactions . Trifunctional antibodies, which bind two antigens (e.g., CD3 and tumor targets), exemplify advanced engineering strategies .
2.1. TIM-3 Antibodies
TIM-3 (T-cell immunoglobulin and mucin domain-3) is a checkpoint inhibitor. Three synthetic human antibodies (DCBT3-4, DCBT3-19, DCBT3-22) derived from a high-diversity scFv library demonstrated:
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Sub-nanomolar binding affinity to TIM-3 recombinant protein .
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Nanomolar inhibition of TIM-3/Galectin-9 signaling in reporter assays .
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Restoration of T-cell proliferation in Galectin-9-treated cultures at 1.3–6.7 nM concentrations .
| Antibody | Binding Affinity (IC₅₀) | Inhibition in Reporter Assay (EC₅₀) | T-Cell Proliferation Restoration (nM) |
|---|---|---|---|
| DCBT3-22 | <1 nM | 7.3 nM | 1.3–6.7 nM |
| MBG-453 | <1 nM | 7.3 nM | 1.3–6.7 nM |
| Human IgG4 | N/A | No effect | No effect |
Data sourced from TIM-3 antibody characterization studies .
2.2. EPHA2-Targeting Antibodies
DS-8895a, an afucosylated anti-EPHA2 IgG1 monoclonal antibody, enhances antibody-dependent cellular cytotoxicity (ADCC) via FcγRIIIa/CD16 binding. Key findings from first-in-human trials:
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Pharmacokinetics: Linear exposure up to 8 mg/kg, with a terminal half-life of ~7 days .
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Efficacy: Targeted solid tumors with EPHA2 overexpression, though clinical response data remain limited .
3.1. Antibody-Dependent Cellular Cytotoxicity (ADCC)
Afucosylation of Fc domains (e.g., DS-8895a) enhances binding to FcγRIIIa/CD16 on NK cells, potentiating ADCC . This mechanism is critical for eliminating tumor cells expressing EPHA2 or other surface antigens.
3.2. T-Cell Activation and Checkpoint Blockade
TIM-3 antibodies disrupt immune suppression by blocking TIM-3/Galectin-9 interactions, restoring T-cell proliferation and antitumor activity . This approach addresses immune exhaustion in chronic infections or cancer.
4.1. Immunogenicity and Anti-Drug Antibodies (ADAs)
ADAs can neutralize therapeutic antibodies, particularly in T-cell-dependent responses. Strategies to mitigate ADA formation include:
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Engineered Fc regions: Afucosylation or GAALIE mutations to modulate effector functions .
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Thermal stability scaffolds: Used in synthetic scFv libraries to reduce immunogenicity .
4.2. Target Localization and Antibody Design
Antibodies targeting stromal antigens (e.g., FAP) versus cellular antigens (e.g., EPHA2) show divergent therapeutic outcomes. For example:
Product Specs
**Constituents:** 50% Glycerol, 0.01M PBS, pH 7.4
