Trainee Spotlight: Tatiana Pazina
Dr. Kerry Campbell lab
I was born in Cheboksary, a small city in Russia, and later moved to St. Petersburg where larger universities and more career opportunities were in abundance. Being ever curious in mathematics and physics, I enrolled in a bioengineering program at Polytechnical University in St. Petersburg, Russia where I discovered a love of research. In fact, I jumped at the chance to participate in an exchange student program to gain experience in a laboratory in the US. In 2010, I joined Dr. Matt Robinson’s lab at Fox Chase Cancer Center to work on a bioengineering project focused on developing carbon nanotube-based antibody-functionalized biosensors for early detection of prostate cancer biomarkers. During my work, I fell in love with the US and realized that I wanted, upon completion of my program, to return to the US to continue my studies. In 2012, I joined the PhD program at the Institute of Experimental Medicine in St. Petersburg, which allowed me to return to Fox Chase Cancer Center to work with Dr. Kerry Campbell. In my current work, we use detailed flow cytometry analyses of blood samples to characterize the phenotypic changes of immune cells in cancer patients. The goals of our research are to predict disease progression, study the efficacy of therapeutic antibodies, and to identify new treatment options. This project has been greatly beneficial to my professional development, as I have learned about immune cell biology and gained extensive experience using flow cytometry. I enjoy translational research and like the idea of working with compounds that will soon have an impact in the clinic. Upon completion of my current projects, I will seek a postdoctoral position in immunology or immunotherapy with the ultimate goal of working on preclinical drug development at a pharmaceutical company.
My research is focused on natural killer (NK) cell responses to multiple myeloma (MM). MM is a B cell malignancy characterized by the expansion of tumor cells in the bone marrow and accumulation of a monoclonal Ig protein in blood and urine, which leads to end-stage organ damage. Despite advances in therapy, MM remains incurable. MM patients usually relapse and die from their disease with an average survival of about 7-8 years from initial diagnosis. Therefore, new approaches for MM treatment are urgently needed.
NK cells are cytotoxic lymphocytes of the innate immune system that facilitate the killing of tumor cells, including myeloma cells. As MM progresses, NK cells become impaired and dysfunctional. However, NK cells of cancer patients can be harnessed, along with monoclonal antibodies, to attack tumor cells. Emerging MM therapies utilize monoclonal antibodies targeted to molecules that are overexpressed on MM cells (e.g. SLAMF7, see below). The main mechanism of action of some of these monoclonal antibodies is NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) through interaction of the antibody with the Fc receptor, CD16, on the surface of NK cells. This interaction leads to NK cell activation and degranulation of cytotoxic molecules from the NK cell toward the tumor cell, which then induces tumor cell death.
Recent investigations have revealed a new therapeutic target, SLAMF7, which is highly and uniformly expressed on MM cells and is also an activating receptor on NK cells. Elotuzumab (Elo) is a new monoclonal antibody that targets SLAMF7 and has been recently approved for MM treatment. My work is focused on studying the effect of Elo on NK cells of MM patients and determining whether Elo can directly activate NK cells through interaction with SLAMF7 on NK cells. We showed that the primary mechanism of action of Elo is ADCC, and we also found that Elo can co-stimulate NK cells via SLAMF7 ligation. In addition, we examined NK cell biomarkers in blood and bone marrow samples from MM patients at various stages of disease by flow cytometry. Our data are highly relevant, since they reveal greater understanding of phenotypic and functional changes in NK cells over the course of disease. Improved understanding of how these changes impact NK cell capacity for ADCC and activation may help identify patient profiles that are likely to benefit from treatment with Elo or other targeted therapies.
Tatiana Pazina, Ashley M. James, Alexander W. MacFarlane IV, Natalie A. Bezman, Karla A. Henning, Christine Bee, Robert F. Graziano, Michael D. Robbins, Adam D. Cohen & Kerry S. Campbell. The anti-SLAMF7 antibody elotuzumab mediates NK cell activation through both CD16-dependant and –independent mechanisms, OncoImmunology, DOI: 10.1080/2162402X.2017.1339853