Presentation description

Chemotherapy is an extremely common and effective treatment for cancer; however, chemotherapy causes patients debilitating side effects including increasing risk of infection, fatigue, nausea, and anemia. One approach to solve these side effects is through the use of targeted drug-delivery systems, such as antibody-drug conjugates (ADCs) which are constructed of a cytotoxic drug chemically attached to a monoclonal antibody. ADCs combine the toxicity of chemotherapy with the specificity of antibodies, allowing for decreased side effects compared to conventional chemotherapy. Despite their potential, ADCs have limitations including off-site effects where the ADs targets its designated antigen on a healthy cell. To combat this problem, we have developed a protease-activated ADC (pADC) to increase cancer cell specificity. Our pADC comprises of the ADC and a blocking peptide which inhibits ADC binding until the construct reaches the tumor microenvironment. Upon entering the tumor microenvironment, the protease-specific linker that attaches the blocking peptide to the AD can be cleaved, reestablishing ADC binding and drug-delivery capabilities. This pADC increases the targeting for cancer cells, thus decreasing off-site effects of cancer therapy.