An Anti-CD33 Antibody-Calicheamicin Conjugate for Treatment of Acute Myeloid Leu

The calicheamicins are highly potent antitumor antibiotics of the enediyne family. Originally isolated from a broth extract of the soil microorganism M. echinospora ssp. calichensis, the calicheamicins were detected in a screen for potent DNA damaging agents. The parent of this family of xenobiotics, calicheamicin 1I, has been shown to associate with the minor groove of DNA and, following reduction with glutathione, to cause sequence-specific, double-stranded DNA cleavage. Due to their unique mode of action and potency, several analogues of the calicheamicins have been tested in preclinical models as potential antitumor agents. Their development as single agent therapies has not been pursued because of delayed toxicities that limit the therapeutic dose range for treatment. However, their potency makes them ideal for antibody-targeted chemotherapy, where limits in antigen expression make the potency of the cytotoxic agent crucial.

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