anti-CD30 antibody-drug conjugate SGN-35T

An antibody-drug conjugate (ADC) composed of brentuximab (cAC10), a chimeric immunoglobuin G1 (IgG1) monoclonal antibody directed against the tumor necrosis factor (TNF) receptor CD30 (tumor necrosis factor receptor superfamily, member 8; TNFRSF8) conjugated, via a protease-cleavable tripeptide linker, comprised of D-leucine-alanine-glutamate (DLAE), to the cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration, anti-CD30 ADC SGN-35T targets, binds to and is internalized by CD30-positive tumor cells. Upon enzymatic cleavage of the cleavable linker, MMAE is released into the cytosol. MMAE binds to tubulin and inhibits tubulin polymerization, which results in G2/M phase arrest and tumor cell apoptosis of CD30-expressing tumor cells. In addition, SGN-35T induces bystander effect in neighboring tumor cells and immunogenic cell death (ICD). CD30 may be constitutively expressed in certain B- and T-cell lymphoma while expression is limited in normal, healthy cells. The linkage system in is highly stable in plasma, resulting in cytotoxic specificity for CD30-positive cells.