Innovative Approaches to Enhance Chimeric Antigen Receptor (CAR) T-Cell Potency Using Quiescent T Cells
Abstract
My ultimate career goal is to advance CAR T cell therapies against cancer. I will combine my expertise in immunology with my engineering skillset to develop the next generation of cell therapies with enhanced efficacy against cancer. I spent the past 8 years learning how to enhance the ability of patients’ immune cells to treat cancer. During the next phase of my career, I will be actively engaged in studies to optimize CAR T cell function, with immediate translational relevance to clinical settings. This next phase of my career will facilitate my long-term plan to utilize the skills I have developed at the University of Pennsylvania to lead my own lab. Given my unique background, I am ideally poised to leverage my interdisciplinary expertise and research experience to become a leading investigator in the field of cancer immunotherapy. Adoptive immunotherapy has demonstrated unprecedented clinical success in the treatment of leukemia and has received US Food and Drug Administration approval. This therapy harnesses the immune system to target cancers. In this therapy, a specific subset of immune cells, T cells, are isolated from a patient, expanded outside of the body in nutrient-rich conditions, and genetically modified prior to reinfusion. The purpose of the genetic modification is to improve their ability to recognize and eliminate cancer cells by expressing a synthetic protein (CAR) on the T cell surface. This CAR confers “specificity” – the ability to recognize cancer cells, and “function” – the ability to destroy those cancer cells. An emerging principle in cellular immunotherapy is to minimize the manipulation of patients’ T cells outside the body. Prolonged culture protocols yield functionally exhausted T cells that limits their survival following re-infusion. Current protocols are also unnecessarily costly and labor intensive. This proposal redefines the CAR T cell manufacturing process; ensuring a rapid generation of CAR T cells without any loss of potency. The latter will be particularly important in bringing these therapies to resource-constrained healthcare settings. The new developments in these studies will also lead to a shorter period of time between blood collection and re-infusion of CAR T cells to patients. This will be of particular benefit to those patients with rapidly progressive disease. This method has immediate clinical relevance and thereby, provides a vertical advance in the field. As the US population, including Veterans, increases and ages, the incidence of cancer steadily increases. In line with the mission of the Department of Defense, the successful completion of the stated goals will increase the availability as well as the therapeutic efficacy of CAR T cells for Veteran patients with cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010417
Entities
People
- Saba Ghassemi
Organizations
- United States Army
- University of Pennsylvania