RE:RE:RE:ONCY pelareorep as a potential bispecific or ADC payload.From failure to success A major advancement in the understanding of the concept of ADCs followed research studies arming antibodies with toxic molecules, such as diphtheria toxin (first proposed in 1970 by Frederick L. Moolten and Sidney R. Cooperband) and radioisotopes. These studies, in which antibodies were conjugated to radioisotopes, initially failed in early clinical development due to an inadequate radiation dose delivered to the tumor site to obtain adequate tumor imaging and clinically meaningful responses. Second generation The realization that more potent payloads could change the future potential of ADCs as a class of therapeutic agents resulted in the development and approval, in early 2000, of gemtuzumab ozogamicin (Mylotarg®; Pfizer). With this approval, the antibody-drug conjugate (ADC) ‘industry’ really started in force. It has taken over two decades since the first cytotoxic antibody-drug conjugate was approved by the FDA, gemtuzumab ozogamicin and the commercial onco-therapeutic ADC market was established.
After more than 20 years of ADC development employing mostly cytotoxins conjugated to monoclonal antibodies or radio-isotopes being chelated to monoclonal antibodies, there are now multiple new approaches and mechanisms of action using antibodies to target diseased cells and tissues to achieve a therapeutic effect.
And when looking forward, cytotoxins (chemotherapy) conjugated to monoclonal antibodies (ADCs) combined with pelareorep + CPI would result in enhanced effectiveness and lower chemotherapy toxicities and adverse side effects.