ANTIBODY-DRUG CONJUGATES FOR CANCER THERAPY

THE AIM OF THIS PROJECT IS TO PRODUCE MONOCLONAL ANTIBODY-DRUG CONJUGATES WITH THERAPEUTIC POTENCY FOR THE SELECTIVE DESTRUCTION OF HUMAN CANCER CELLS. IT IS STATED THAT ANTIBODY-DRUG CONJUGATES PREPARED BY CURRENT APPROACHES DO NOT ACHIEVE HIGH LEVELS OF FREE DRUG INSIDE TARGETED CELLS. WE WILL REPLACE THE CURRENT MODERATELY CYTOTOXIC ANTI-CANCER DRUGS WITH MAYTANSINOIDS WHICH ARE 100 TO 1000 FOLD MORE CYTOTOXIC. THE MAYTANSINOIDS WILL BE LINKED VIA DISULFIDE BONDS, WHICH ARE STABLE IN CIRCULATION, BUT CLEAVED INTRACELLULARLY. THE MAYTANSINOIDS WILL BE SYNTHETICALLY MODIFIED TO INCORPORATE DISULFIDE OR THIOL GROUPS. THE MOST CYTOTOXIC OF THESE DRUGS WILL BE CONJUGATED TO MONOCLONAL ANTIBODIES BY DISULFIDE BONDS AND ASSESSED FOR IN VITRO CYTOTOXICITY TO CANCER CELLS. IN VIVO PHARMACOKINETIC PROPERTIES WILL BE EVALUATED IN MICE.