Bladder Cancer Therapy

About

BACKGROUND Bladder cancer is a common form of cancer, which progresses by spreading into surrounding muscle. This advanced stage, called muscle invasive bladder cancer (MIBC), is associated with poor prognosis due to a lack of effective treatment options. Currently, treatment is restricted to the surgical removal of cancerous tissue combined with radiotherapy and/or chemotherapy, which are both associated with severe side-effects as they affect both cancerous and noncancerous cells. In addition, determining the appropriate therapeutic regime for bladder cancers is hampered by a lack of accurate imaging technology. Antibody-drug conjugates (ADCs) use the specificity of antibodies to target only cancerous cells with a therapeutic agent. We are therefore developing a targeted ADC for MIBC. TECHNOLOGY The interleukin-5 receptor (IL5-Rα) has been identified as a biomarker of advancing bladder cancer. Therefore, cells expressing IL5-Rα can be targeted by ADCs for treatment. We have developed a monoclonal antibody (mAb), that has been conjugated with a chemotherapeutic agent. In addition these mAbconjugates have been packaged with additional structural technology for enhanced cellular accumulation in IL5-Rα (CD125)-positive MIBC cells. We have validated the target for expression and internalisation and shown that the ADC is efficacious in human cancer cells. A radiolabelled Immunoconjugate (RIC) has also been generated that could be used for diagnostic purposes to accurately determine the extent of the cancer prior to undertaking a treatment plan.