Microfluidic systems to study immunotherapy-resistant tumors.
Since their FDA approval, immune checkpoint inhibitors have delivered durable responses for many patients with various cancers including melanoma and lung cancer. Utilization of anti-PD1, anti-PDL1 and anti-CTLA4 monoclonal antibodies have demonstrated great promises in a select group of patients who are positive for the respective biomarkers. Moreover, there are several combination therapies in clinical trials which try to extend the use of these checkpoint inhibitors to benefit those patients who are resistant to monotherapies with these antibodies. However, a new pattern of response has been recently observed by many groups in patients who are considered to be eligible to receive any of the checkpoint inhibitors. It has been demonstrated that a sub-population of patients who receive immune checkpoint inhibitor treatment not only their tumors does not shrink, but they, in fact, experience a distinct pattern of tumor hyper progression under immunotherapy. To date, several genetic alternations as well as involvement of antibody characteristics have been shown to be associated with hyper progression, however, much research is still needed to demonstrate the level of contributions of these alterations and characteristics to the aggressive tumor growth observed in these sub-population of patients. To this end, Microfluidic systems present a valuable platform for in-depth analysis and validation of potential contributing factors to hyper progression disease ex-vivo. Our group is currently investigating utilization of microfluidic systems for ex-vivo analysis of these tumors with the hope of being able to better select patients who may potentially be at higher risk of experiencing hyper progressive disease under immunotherapy.
Ehsan Sarafraz-Yazdi, PhD/MPH, is the Founder, Board Director and Chief Executive Officer of NomoCan Pharmaceuticals, an oncology drug development company based in New York City. Prior to starting NomoCan, he was an Assistant Professor and translational research principle investigator at the Division of Gynecologic Oncology, State University of New York, Downstate Medical Center. As a cancer-geneticist and molecular biologist, he has extensive experience in the field of cancer biomarker discovery and therapeutics. His research has been recognized by various awards including “Outstanding Clinical Scholar” award from the AACR/GlaxoSmithKline as well as by the Robert Furchgott Society (Nobel Prize in Medicine, ’98). He received his Ph.D. in Cellular and Molecular Biology and M.P.H. in Health Policy and Management from SUNY Health Science Center- NY and his M.Sc. in Applied Genetics from University of Birmingham and Imperial College of London- U.K.