Researcher Spotlight: Antonia Rotolo, MD, PhD

University of Pennsylvania Perelman School of Medicine

Researchers are seeking ways to expand the effectiveness of chimeric antigen receptor (CAR) T-cell therapy to lymphoma subtypes for whom the most common type of CAR therapy, CD19 CAR T-cell, is not effective due to a lack of the CD19 biomarker. In T-cell lymphomas, the biomarker CD5 is extremely common; unfortunately, it is found not just on malignant T-cell lymphoma cells, but on normal T-cells in the immune system. In order to avoid eradicating both “good” T-cells and T-cell lymphoma cells with a CD5 CAR T-cell therapy, Dr. Rotolo and her colleagues have developed a process to remove the CD5 biomarker from the “good” cells, creating
cells they call CD5 Knock Out (or CD5KO) T-cells. “We can tweak the ‘good’ T cells not to express CD5 (CD5KOT), thus making them ‘invisible’ to CART5 cells, and co-inject CART5 cells to eradicate the tumor with CD5KOT cells to ensure concomitant protection against pathogens,” Dr. Rotolo says. “Upon disease eradication, CART5 cells can be eliminated to allow recovery of the endogenous ‘good’ T cells and long-term restoration of normal T cell immunity.”

Dr. Rotolo received her MD from the University of Torino in her native Italy, where she also completed a residency and hematology fellowship before an additional fellowship at Imperial College London Hammersmith Hospital. While in London, she was offered an opportunity to study the development of novel therapeutic strategies for relapsed/refractory lymphoma patients. “It was 2013, a number of exciting reports were suggesting that CAR T-cells could potentially cure B-cell lymphoma patients where all available treatments had previously failed,” she says. “Hence, in 2014 I enrolled in a PhD program at Imperial College London and committed to research in the field of CAR immunotherapy.” Upon completing her PhD, Dr. Rotolo became a Postdoctoral Fellow at the University of Pennsylvania in order to work with CAR T-cell pioneer Carl June, MD, and her Fellowship sponsor, Marco Ruella, MD.

Dr. Rotolo says receiving the LRF Postdoctoral Fellowship Grant will aid her career development as an independent researcher. “Thanks to LRF support, I will be able to continue working at Penn and move forward my research project. Given the strong translational connotation of my project and the vibrant scientific environment of my Institution, I also anticipate that my LRF funded postdoc will be of great educational value and will enormously impact my academic career.”