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Matthew Campbell, MD
Chief Fellow, Hematology/Oncology Fellowship, UT MD Anderson Cancer Center

New agents called immune check point inhibitors have been FDA approved in the treatment of metastatic melanoma and metastatic squamous cell lung cancer. These agents have shown exciting activity in bladder, kidney, and a variety of other cancers in early clinical studies and are being explored in larger studies. The first of these agents, ipilimumab, is an antibody that binds to CTLA-4, a molecule that is increased by T cells responding to a stimulus, to help shut off the immune response. When the anti-body binds to CTLA-4, the immune system is able to stay activated and recognize a cancer cell as foreign targeting it for destruction. A similar agent to ipilimumab is tremelimumab. Agents targeting CTLA-4 have produced a response in 10-15% of patients treated with the majority of these patients having a very long-lasting response. Our group has identified that patients with bladder and prostate cancer treated with ipilimumab have increased numbers of T cells expressing high levels of the inducible costimulator (ICOS). In a retrospective analysis, patients with metastatic melanoma with a sustained high level of ICOS expressing T cells were found to have superior survival. Cryosurgery is a minimally invasive procedure that places a metal probe in a tumor allowing the delivery of liquid nitrogen freezing tumor tissue while sparing normal surrounding tissue. Cryosurgery kills cells in a variety of different ways with certain cells undergoing a complete bursting (necrosis) or through a programmed cell death (apoptosis). Cryosurgery can be performed on small tumors in a variety of anatomical locations. Cryosurgery has also been associated with the “Abscopal effect”, which refers to treating one tumor and seeing an untreated tumor in a separate part of the body shrink or disappear. Though the mechanism is unclear, the immune system is implicated. Preclinical animal studies in both melanoma and prostate cancer have found the combination of cryoablation and anti-CTLA-4 more effective than either treatment alone in protecting animals from tumor rechallenge and death from cancer. With this knowledge, a pilot study in metastatic renal cell carcinoma has been proposed. In the study, a group of patients will receive two doses of tremelimumab followed by cytoreductive nephrectomy (removal of the kidney with tumor despite the presence of metastatic disease). A second group of patients will have cryoablation of a metastatic lesion followed by two doses of tremelimumab and cytoreductive nephrectomy. A third group of patient will have cytoreductive nephrectomy alone (control). Our hypothesis is that using cryoablation with tremelimumab will be more effective than tremelimumab or no treatment in increasing the frequency of ICOS expressing T cells both in the tumor tissue and in the systemic circulation (bloodstream). We hypothesize patients with an increased frequency of ICOS expressing T cells in the systemic circulation and within the tumor will have an increased anti-tumor effect found at the time of nephrectomy. My first aim is to ensure the safety of cryoablation with tremelimumab, and we will tabulate the side effect profile of each treatment arm. My second aim is to study both the tumor tissue and blood samples prior to treatment, during treatment, and after treatment to understand if changes in the immune system are detected that may predict if certain patients are more likely to benefit from this approach than others. 

Biography 
Five years ago I was diagnosed with melanoma in situ on my cheek. After the stress, subsequent surgeries, and a look in the mirror, I knew I wanted to enter into cancer based research. During my time in Indiana, I had the wonderful opportunity to work in a basic science laboratory. I successfully published two first author papers focusing on inflammation and innate immunity in a renal obstruction model and collaborated on several other efforts. I learned the tremendous dedication, attention to detail, and work ethic required to be successful in medical research. After my time in the laboratory, my clinical training was in internal medicine at Indiana University and now in medical oncology at MD Anderson Cancer Center. I have served as chief medicine resident and currently serve as the chief fellow of the hematology/medical oncology fellowship at MD Anderson. Since my arrival in Houston, I have dedicated myself to a career in translational genitourinary medical oncology. I have worked closely with Drs. Nizar Tannir, Arlene Siefker-Radtke, and Padmanee Sharma. I have published the results of a phase I clinical trial, served as the second author on a phase II clinical trial which has been submitted for publication, built a comprehensive dataset of 220 patients who have survived for greater than 4 years with metastatic renal cell carcinoma and presented this work in poster form at the 2015 Genitourinary Cancer Symposium, written a clinical protocol at the ASCO/AACR Vail conference, participated in a master’s of science program dedicated for clinical and translational researchers, and worked in Dr. Padmanee Sharma’s laboratory group collaborating on several projects. Under Dr. Sharma’s mentorship, I have learned important skill sets needed to perform my Conquer Cancer Foundation Young Investigator Award project. I am committed to a career in translational research in cancer immunotherapy, especially as it relates to renal and bladder malignancies, and have dedicated my fellowship to try and equip myself with the tools needed to succeed down this pathway. I plan on joining the MD Anderson Cancer Center Department of Genitourinary Medical Oncology upon my graduation this upcoming June.