A chemically defined trifunctional antibody-cytokine-drug conjugate with potent antitumor activity.

A chemically-defined trifunctional antibody-cytokine-drug conjugate with potent anti- tumor activity Running Title: An antibody-cytokine-drug conjugate with anti-tumor activity

Specificity of Tumor Cell Killing Immunoconjugates Compared with Free Adriamycin and Antitumor Activity of Adriamycin (Hydrazone-linked)

Adriamycin (ADM) was chemically coupled to two monoclonal anti bodies (MAb) expressed on human B-cell lymphomas. Immunoconju gates were prepared by linking to the MAb an ADM derivative, Adria mycin 13-|3-(2-pyridy)dithio)propionyl]hydrazone (ADM-HZN), which releases ADM under mild acidic conditions (see preceding article). The (ADM-HZN) conjugates were tested for antitumor activity on two human...

Antitumor activity of adriamycin (hydrazone-linked) immunoconjugates compared with free adriamycin and specificity of tumor cell killing.

Adriamycin (ADM) was chemically coupled to two monoclonal antibodies (MAb) expressed on human B-cell lymphomas. Immunoconjugates were prepared by linking to the MAb an ADM derivative, Adriamycin 13-[3-(2-pyridyldithio)propionyl]hydrazone (ADM-HZN), which releases ADM under mild acidic conditions (see preceding article). The (ADM-HZN) conjugates were tested for antitumor activity on two human B-...

Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate.

PURPOSE An antibody-drug conjugate consisting of monomethyl auristatin E (MMAE) conjugated to the anti-CD30 monoclonal antibody (mAb) cAC10, with eight drug moieties per mAb, was previously shown to have potent cytotoxic activity against CD30(+) malignant cells. To determine the effect of drug loading on antibody-drug conjugate therapeutic potential, we assessed cAC10 antibody-drug conjugates c...

Engineered antibody-drug conjugates with defined sites and stoichiometries of drug attachment.

The chimeric anti-CD30 IgG1, cAC10, conjugated to eight equivalents of monomethyl auristatin E (MMAE) was previously shown to have potent antitumor activity against CD30-expressing tumors xenografts in mice. Moreover, the therapeutic index was increased by lowering the stoichiometry from 8 drugs/antibody down to 2 or 4. Limitations of such 'partially-loaded' conjugates are low yield (10-30%) as...