SD17 Antibody

Target Overview: ADAM17

ADAM17 (A Disintegrin and Metalloproteinase 17) is a transmembrane protease regulating inflammation, immunity, and viral entry by cleaving substrates like TNF-α, ACE2, and IL-6R . Its dual role in promoting inflammation and modulating viral replication makes it a critical therapeutic target.

Antibody Structure and Mechanism

ADAM17-targeting antibodies like MEDI3622 are IgG1 monoclonal antibodies with kappa light chains . Key features:

• Binding Specificity: Blocks ADAM17’s catalytic site, inhibiting ectodomain shedding of substrates (e.g., TNF-α, ACE2) .

• Biological Impact:

  • Reduces pro-inflammatory cytokines (TNF-α, IL-6) .

  • Modulates ACE2 shedding, affecting SARS-CoV-2 entry .

Sepsis

• Preclinical Outcomes:

  Parameter	MEDI3622-Treated Mice	Control (Saline)
  Mortality Rate	20% reduction	40% mortality
  Bacterial Clearance	3x higher neutrophil recruitment	Baseline
  Cytokine Levels	TNF-α reduced by 60%	Elevated
  MEDI3622 synergized with antibiotics, enhancing survival by 70% in polymicrobial sepsis models .

COVID-19

• Mouse Model Results:

  • Morbidity: MEDI3622-treated mice lost 8% less weight vs. controls .

  • Viral Burden: Lung viral RNA increased 2.5x post-treatment, suggesting reduced inflammation at the cost of viral persistence .

  • Histopathology: 50% less lung inflammation vs. saline controls .

Oncology

• CD8+ T Cell Modulation: ADAM17 inhibition elevated CD122 expression, enhancing IL-2/IL-15 responsiveness and CAR-T efficacy in solid tumors .

Comparative Efficacy in Disease Models

Clinical and Technical Challenges

• Trade-offs: ADAM17 blockade reduces inflammation but may impair viral clearance (e.g., SARS-CoV-2) .

• Specificity: MEDI3622 avoids off-target effects seen with small-molecule MMP inhibitors .

• Dosing: Optimal timing (pre- vs. post-infection) critically affects outcomes .

Future Directions

• Combination Therapies: Pairing MEDI3622 with antivirals or checkpoint inhibitors to balance inflammation and pathogen control .

• Biomarker Development: Correlating ADAM17 activity with sepsis progression or COVID-19 severity .