APUM26 Antibody
Description
Overview of AFM26 Antibody
AFM26 is a bispecific tetravalent antibody engineered to target BCMA (B-cell maturation antigen) on multiple myeloma (MM) cells and CD16A (FcγRIIIa) on natural killer (NK) cells. Developed by Affimed GmbH, it is designed to bridge NK cells with tumor cells, enhancing cytotoxicity against BCMA-positive malignancies .
Key Features:
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Structure: Bispecific format with two binding domains for BCMA and two for CD16A, enabling high-avidity interactions.
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Mechanism: Redirects NK cells to lyse MM cells via antibody-dependent cellular cytotoxicity (ADCC) without depleting NK cells .
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Differentiation: Unlike BCMA-targeting T-cell engagers (e.g., bispecific T-cell engagers), AFM26 avoids cytokine release syndrome risks by focusing on NK cells .
In Vitro Efficacy
AFM26 demonstrated potent lysis of MM cells, including those with low BCMA expression, and retained activity in high-serum IgG environments . It also showed no NK cell depletion, a critical safety advantage .
In Vivo Models
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Primate Studies: AFM26 reduced tumor burden in MM xenograft models at doses as low as 0.25 mg/kg .
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Combination Potential: Synergized with adoptive NK cell therapies to eliminate minimal residual disease post-stem cell transplantation .
Clinical Relevance
AFM26 addresses unmet needs in MM treatment by:
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Overcoming Resistance: Targets BCMA-independent pathways via NK cell activation.
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Safety Profile: Avoids T-cell-related toxicities (e.g., neurotoxicity) common with CD3-targeting bispecifics .
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Broad Applicability: Effective against heterogeneous BCMA expression, a limitation of CAR-T therapies .
Comparative Analysis with Other BCMA-Targeting Antibodies
| Antibody | Target(s) | Effector Cells | Clinical Stage | Key Limitation |
|---|---|---|---|---|
| AFM26 | BCMA × CD16A | NK cells | Preclinical | Limited data in solid tumors |
| Teclistamab | BCMA × CD3 | T cells | Approved | Cytokine release syndrome |
| Belantamab | BCMA (ADC) | N/A | Approved | Ocular toxicity |
AFM26’s NK cell focus positions it as a safer alternative to T-cell-centric therapies .
Future Directions
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
Q&A
Based on a comprehensive review of available literature and emerging technologies in antibody research, here's a curated FAQ addressing key methodological considerations for working with novel antibodies like APUM26:
Advanced Research Challenges
3. Resolving contradictory binding data between ELISA and SPR
When surface-based (ELISA) and solution-phase (SPR) assays disagree:
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Check epitope accessibility: Immobilization may mask conformational epitopes
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Test buffer ionic strength: High salt (>150mM NaCl) can disrupt weak interactions
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Perform temperature gradient analysis (4-37°C) to assess entropic contributions
4. Optimizing antibodies for multiplexed detection systems
For integration with platforms like AIMDx :
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Engineer biotinylation tags using BirA ligase system
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Validate thermal stability (Tm ≥65°C via DSF)
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Test cross-talk thresholds in multiplex panels:
| Multiplex Tier | Allowable Cross-Reactivity | Validation Method |
|---|---|---|
| 10-plex | ≤0.1% | Luminex bead array |
| 50-plex | ≤0.01% | DNA-barcoded SomaScan |
Emerging Methodologies
5. Implementing AI-driven antibody optimization
The JAM framework demonstrates successful de novo design through:
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Epitope-focused libraries with RosettaAntibodyDesign
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In silico maturation using molecular dynamics (≥100ns simulations)
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Developability prediction via SCORCH metrics (aggregation score <20%)
6. Advanced epitope mapping techniques
Beyond traditional peptide arrays:
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Hydrogen-deuterium exchange MS: Resolution <5Å
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Cryo-EM single-particle analysis: Achieves 3-4Å localization
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Deep mutational scanning: Profile all single AA variants in parallel
Data Interpretation Framework
For conflicting functional data (e.g., neutralization vs enhancement):
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Perform FcγR binding profiling to identify effector function biases
Key statistical considerations:
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Apply Benjamini-Hochberg correction for high-throughput screens
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Report effect sizes with 95% confidence intervals
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Archive raw flow cytometry files in FCS 3.1 format
