Using the Lessons Learned from the Clinic to Improve the Preclinical Development of Antibody Drug Conjugates

Abstract

The treatment options for cancer patients include surgery, chemotherapeutics, radiation therapy, antibody therapy and various combinations of these therapies. The challenge with each therapy is finding the balance between maximizing the anti-tumor efficacy while minimizing the dose limiting toxicities. Antibodies, unlike small molecule chemotherapeutics, selectively bind to cell surface tumor antigens and can be used to deliver radionucleotides or small molecule chemotherapeutic drugs directly to the tumor. Advances in antibody engineering, linker chemistry and the identification of potent cytotoxic drugs led to the recent approval of two antibody drug conjugates to treat breast cancer and lymphoma patients. We will discuss how the observations from the clinical development of antibody drug conjugates can guide the preclinical development of the next generation of antibody drug conjugates.