ADAM10 (A Disintegrin And Metalloproteinase 10) is a transmembrane protease involved in ectodomain shedding of proteins like Notch, amyloid precursor protein (APP), and cytokines. Antibodies targeting ADAM10 are critical tools for studying its roles in cancer, Alzheimer's disease, and immune regulation.
B Cell Regulation: ADAM10 deficiency in B cells (ADAM10<sup>B-/-</sup> mice) causes impaired germinal center formation, reduced follicular Th cells, and altered lymph node structures, significantly diminishing antibody responses to T-dependent antigens .
Cancer Targeting: The 8C7 monoclonal antibody selectively binds active ADAM10 conformers on tumor cells. Conjugated to cytotoxic drugs, it inhibits xenograft growth in mice while sparing normal tissues .
Mechanistic Insights: ADAM10 modulates B cell localization and chemokine expression in lymphoid tissues, establishing it as a master regulator of humoral immunity .
AG10 is an oral small-molecule kinetic stabilizer of transthyretin, not an antibody. It shows promise for treating transthyretin amyloidosis (ATTR).
Mechanism: Binds tetrameric TTR with negative cooperativity (K<sub>d1</sub>=0.7 μM, K<sub>d2</sub>=75 μM), preventing dissociation into amyloidogenic monomers .
Efficacy: Completely inhibits acid-mediated dissociation of pathogenic V122I-TTR mutants at 10 μM .
Safety: No hepatic/renal toxicity observed in phase 1 trials (up to 800 mg doses) .
Here’s a structured collection of FAQs tailored for academic researchers working with ADAM10 antibodies, based on analysis of peer-reviewed methodologies and experimental data from diverse sources:
Post-translational modifications: Glycosylation or cleavage (e.g., 120 kDa precursor → 90 kDa active form) .
Protease inhibitors: Include in lysis buffers to prevent artifactual degradation.
Alternative isoforms: Test splice variants using isoform-specific primers .
Threshold effects: Anti-GM1 antibodies with KD <1 nM induced neuropathy vs. >10 nM in controls .
Context dependence: High affinity may hinder tissue penetration; balance with valency (e.g., IgG vs. Fab fragments) .
Unexpected bands: Re-run with KO controls (e.g., 19 kDa band in ab124695 may indicate degradation) .
Stabilization metrics: Use ≥90% threshold (as in AG10’s TTR stabilization) for clinical relevance .
Affinity maturation: Compare recombinant vs. hybridoma-derived antibodies (1–2 log KD differences) .