A novel strategy for treatment of bladder cancer: Antibody-drug conjugates

Abstract

In the past, there was no second-line chemotherapeutic agent suitable for use when urothelial carcinoma (UC) progressed to platinum-resistant UC. However, recently, several new treatment options, such as immune checkpoint inhibitors or targeted therapy have shifted the treatment paradigm regarding second-line therapeutic modalities. A novel class of therapeutic agents includes an antibody-drug conjugate (ADC). ADCs consist of three characteristics: a monoclonal antibody, linker, and payload. The specificity of the monoclonal antibody facilitates the delivery of a linked cytotoxic drug directly into the target tumor cell. Although various ADCs have been developed and approved for use in treating several solid tumors, almost all ADCs for the treatment of UC are still in the testing phase. Here, we review the key points about ADCs and summarize the novel ADCs that are approved or are involved in ongoing studies in UC.

Keywords: Antibody-drug conjugate; Bladder cancer; Immunoconjugates; Immunotherapy; Urinary bladder neoplasms.

Fig. 1. Antibody-drug conjugate structure consisting of monoclonal antibody, linker, and cytotoxic payload. The antibody is specific to tumor cell surface proteins. The linker is the chemical connector that binds the drug to the antibody. The payload is a highly potent cytotoxic drug. Fab, fragment antigen binding; Fc, fragment crystallizable.

Fig. 2. Illustration of the mechanism of action of antibody-drug conjugates (ADCs). ADCs bind to the surface antigen on tumor cells. Subsequently, ADCs are internalized through receptor-medicated endocytosis. ADCs are processed through the endosome-lysosome pathway leading to release of the cytotoxic payload and induced tumor cell death by attacking DNA or affecting microtubule structure.