Several groups hypothesized that it may be necessary to construct ADCs with drugs of much higher molar potencies than conventional chemotherapeutics to achieve therapeutically effective levels of active drug within tumors in patients. A major advance in ADC technology came with the utilization of such highly potent drugs as calicheamicins, maytansinoids, auristatins, and CC1065 analogs. This progress reflects an appreciation that the localization of antibodies to tumors is inefficient in man: typically 0.0003%-0.08% injected dose per gram of tumor.