Practice question
Question
Brentuximab vedotin targets:
Explanation
CD30 antigen also designated TNFRSF8, 120 kDa type I transmembrane glycoprotein member tumor necrosis factor receptor superfamily characterized by cysteine rich domains extracellularly and TRAF binding motifs intracellularly activating NF-kB, transiently expressed on activated B and T lymphocytes but constitutively highly expressed on Reed-Sternberg giant cells of classical Hodgkin lymphoma and anaplastic large cell lymphoma ALCL, and small subset cutaneous T cell lymphomas, making near tumor specific target with minimal normal tissue expression limited to activated immune cells conferring favorable safety margin. Brentuximab vedotin pioneered antibody-drug conjugate class, comprising chimeric anti-CD30 IgG1 antibody cAC10 variable regions murine grafted onto human constant selected for high internalization rate, conjugated via protease-cleavable valine-citrulline dipeptide plus PABC self-immolative spacer to monomethyl auristatin E synthetic analogue of marine natural product dolastatin 10 derived from sea hare Dolabella auricularia that binds tubulin at vinca domain inhibiting polymerization. This mechanistic insight supports diagnostic and therapeutic applications while reinforcing core immunological and cell biology principles taught in advanced curricula.
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