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Anti-S. aureus ClfA (Tefibazumab)-SPDB-DM4 ADC (ADC-W-2133)

This ADC product is comprised of an anti-S. aureus ClfA monoclonal antibody conjugated via a SPDB linker to DM4. The DM4 is targeted to certain cancers by immunerecognition and delivered into cancer cells via receptor mediated endocytosis. Within the cell, DM1 binds to tubulins, interrupts microtubule dynamics, and subsequently, induces cell death.

 ADC Target

  • Name
  • S. aureus ClfA
  • Alternative Names
  • S. aureus ClfA
  • Overview
  • S. aureus may occur as a commensal on skin; it also occurs in the nose frequently (in about a third of the population) and the throat less commonly; S. aureus can infect other tissues when barriers have been breached. S. aureus infections may spread through contact with pus from an infected wound, skin-to-skin contact with an infected person by producing hyaluronidase that destroys tissues, and contact with objects such as towels, sheets, clothing, or athletic equipment used by an infected person. Deeply penetrating S. aureus infections can be severe. ClfA is a 92 kDa surface protein identified from S. aureus. ClfA is responsible for the fibrinogen-dependent c1umping of bacteria.

 ADC Antibody

  • Overview
  • Humanized Anti-S. aureus ClfA IgG1-kappa antibody, Tefibazumab
  • Generic name
  • Tefibazumab
  • Host animal
  • Mouse

 ADC Linker

  • Name
  • SPDB (N-succinimidyl-4-(2-pyridyldithio)butyrate)
  • Description
  • Disulfide Linkers, are extensively exploited as a chemically labile linkage. Since the release of disulfide-linked drugs requires a cytoplasmic thiol cofactor, such as glutathione (GSH). Disulfides maintain stable at physiological pH and only when ADCs are internalized inside cells, the cytosol provides reducing environment including intracellular enzyme protein disulfide isomerase, or similar enzymes, drugs can be released.

 ADC payload drug

  • Name
  • DM4 (N2'-Deacetyl-N2'-(4-mercapto-4-methyl-1-oxopentyl)maytansine)
  • Description
  • Derived from Maytansinoid,a group of cytotoxins structurally similar to rifamycin, geldanamycin, and ansatrienin. The eponymous natural cytotoxic agent maytansine is a 19-member lactam (ansa macrolide) structure originally isolated from the Ethiopian shrub Maytenus ovatus. Maytansinoids can bind to tubulin at or near the vinblastine-binding site, which interfere the formation of microtubules and depolymerize already formed microtubules, inducing mitotic arrest in the intoxicated cells.

For Research Use Only. NOT FOR CLINICAL USE.

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