Antibody Drug Conjugates for Cancer Therapy – From Early Stage Research to a Clinically Approved Drug
Vice President, Chemistry and Senior Distinguished Fellow
February 9, 2017
12:30 p.m. - 1:20 p.m.
Foege N130A, Wallace H. Coulter Seminar Room
Monoclonal antibodies (mAbs) have played a major role in cancer medicine, with active drugs such as trastuzumab (Herceptin), cetuximab (Erbitux), bevacizumab (Avastin) and rituximab (Rituxan) in a wide range of therapeutic applications. The mechanisms of these agents involve such activities as direct signaling, interactions with Fc? receptors on effector cells, and complement fixation. Several approaches have been explored to improve antibody-based therapies for cancer treatment by optimizing such activities and by conscripting their selectivity profiles for the delivery of high potency cytotoxic drugs. The field has advanced significantly in the past few years, with the approval of Adcetris (brentuximab vedotin) for the treatment of relapsed Hodgkin and anaplastic large cell lymphomas. The drug is comprised of a potent antimitotic agent, monomethyl auristatin E (MMAE), conjugated to an anti-CD30 mAb through a lysosomally cleavable dipeptide linker. The inspiration behind the ADC cytotoxic component came from the marine natural product, dolastatin 10. This presentation will describe the discovery and development of Adcetris, and will overview advancements in the field of ADCs for cancer therapy.
Dr. Senter was one of the original scientists at Seattle Genetics, and built up research groups in the areas of monoclonal antibodies and drug conjugates for cancer therapy. His group developed the technology that was used in brentuximab vedotin, a clinically approved antibody drug conjugate for the treatment of various lymphomas. He was one of the original inventors of Etopophos, a clinically approved anticancer drug, and has contributed the technology for many anticancer drugs that are in various stages of clinical development. His research spans an array of topics of relevance to the field of antibodies as drugs, including protein chemistry, antibody engineering, anticancer drug chemistry, and novel linker development.