Microtubule inhibitor-based antibody-drug conjugates for cancer therapy.

Overview

The specificity of monoclonal antibodies represents a potential therapeutic advantage, but their use as single agents in oncology has proven limited to date. The development of antibody-drug conjugates (ADCs) takes advantage of the specificity of the monoclonal antibody and potent cytotoxic effect of chemotherapy, leading to enhanced cytotoxicity in target cells and limiting toxicity to normal tissue. Microtubules represent a validated oncologic target in a range of tumor types, with a number of anti-microtubule targeting cytotoxic drugs approved for cancer use. The systemic use of potent microtubule-binding agents is limited by their effects in normal cells, which leads to toxicity including myelosuppression and peripheral neuropathy. Linking these agents to monoclonal antibodies may limit toxicity to normal tissues and increase drug concentration in target tissues, also allowing the use of more potent agents which would be too toxic to administer in their unbound form. Two such ADCs have been approved for clinical use and many others are in development. Here we review the characteristics of each of the ADC components that have led to efficacious therapies and discuss some of the tubulin inhibitor-based ADCs in development for cancer therapy.