Aiming for a clinical breakthrough to activate patients’ immune system against malignancies of the thoracic cavity

Ori Wald, M.D, Ph.D. Department of Cardiothoracic Surgery.

Malignancies of the thoracic cavity are highly aggressive cancers arising from the various tissues and organs in the chest cavity. Two such aggressive cancers are lung cancer and malignant pleural mesothelioma (MPM). Lung cancer is the second most common malignancy and by far the leading cause of cancer deaths among both men and women. According to the American Cancer Society, each year, over 154,000 deaths are attributed to lung cancer. Survival in people with lung cancer varies, depending on the stage (extent) of the cancer when it is diagnosed. Unlike lung cancer, MPM, is a relatively rare cancer that is often related to asbestos exposure. Nonetheless, MPM is usually fatal even if diagnosed at early stages of the disease. In the U.S. alone, the incidence of MPM is estimated to be about 3,300 cases per year, although it is expected to continue rising internationally. Unfortunately, both lung cancer and MPM are often diagnosed late in the course of the disease, when a cure is no longer a realistic goal. In fact, over 75% of these cancers are diagnosed when the primary tumor has already spread. Current therapy includes removal of the tumor cells through chemotherapy, radiation and surgery, as well as through the use of drugs called immune checkpoint inhibitors (ICI), which are aimed at enhancing the response of the patient’s own immune system against the remaining tumor cells. And yet, although ICI has shown some promising results in lung cancer and MPM, the response rate (around 25%) and the duration of response (3-12 months) remain far from satisfactory.

Dr. Wald’s research concentrates on extending the efficacy of current anticancer treatments through the development of novel methodologies that will tilt the balance toward a robust anti-tumor immune response. To this end, his research focuses on a unique family of proteins and receptors called chemokines and chemokine receptors, which are known to be involved in controlling the movement of a wide variety of immune cells, thus triggering and augmenting the response of a patient’s own immune system against the tumor. These features endow chemokines with crucial roles in immune responses and, importantly, can pave the way to develop a novel type of anticancer treatment. Dr. Ori Wald, an accomplished cardiothoracic surgeon, builds on his medical and surgical expertise to develop sophisticated, accurate and immune-competent disease models to test how inhibiting or augmenting the signaling of specific members of this chemokine family affects the response of the immune system against the tumor.

Dr. Wald and his research team are in a unique translational position to uncover key therapeutic targets and disease-changing agents as they perform their experiments under conditions that properly mimic the propagation of human disease and in combination with drugs that are currently used in the clinic. His ultimate research aim is to translate findings taken from his basic research into clinical medical practice that would have meaningful health outcomes to improve the wellbeing of patients affected by these deadly diseases. Indeed, his multidisciplinary approach is especially noteworthy given Dr. Wald’s ability to pull together all the critical components of his research and clinical training to translate his findings from the laboratory into early phases of clinical trials, aiming for true clinical breakthroughs to combat these dismal cancerous diseases.

Dr. Wald joins a new breed of outstanding entrepreneurial physician/researchers at Hadassah who bring a unique perspective to defeating aggressive cancers. He has recently spent a year as an Instructor of Surgery in the Division of General Thoracic Surgery at Baylor College of Medicine in Houston, Texas. He uses his experience as a superb physician/surgeon and researcher to advance the science of medicine from the bench to bedside clinical implementation. Dr. Wald has published in leading peer-reviewed medical journals and has acted as an advisor to several biotech companies. He has also received numerous awards, including the Morasha Early Career Grant and Hadassah’s Young Investigator Prize.