Mentor Areas
- Immuno-oncology
- Model development
- GBM biology
Description:
Glioblastoma (GBM), glioma grade IV, is a devastating cancer with an annual incidence of 3.19/100,000 individuals per year (~10,000) and a median survival of ~16 months following standard-of-care surgery, radiotherapy, and chemotherapy. Few advances in treatment have been realized over the past 20 years, and 2-year survival remains close to 25%. We are developing novel methods for treating GBM and improving the outcomes of patients with this devastating disease. Our research focuses on several areas of immuno-oncology, supported by model establishment and development. Our immuno-oncology work takes advantage of the patient's own immune system. Through cell engineering approaches, we modify T cells, NK cells, macrophages, and other immune cells to recognize and attack the tumor. Current work focuses on expanding our targeting repertoire, adding armoring constructs to enhance persistence, and exploring combination therapy approaches.
In parallel, we conduct correlative studies on patient samples from ongoing clinical trials. Evaluation of tissue, blood, and cerebrospinal fluid from patients undergoing experimental therapy provides us the opportunity to evaluate what is actually happening in the patients and how well it works. This information is then used to inform and direct ongoing therapy development in the lab.
An adaptive immunosuppressive microenvironment is a major barrier to immune-based therapies for solid tumors, including glioblastoma (GBM). Current model systems for preclinical development either lack substantial components of the immune system or rely upon different species’ immune systems, which display significant differences when compared to human immune systems. These deficiencies lead to the disconnect between preclinical and clinical research. In my lab, we are developing a humanized mouse system for the study of immune system interactions with GBM. By taking hematopoietic stem cells from a GBM patient, we can engraft the human immune system in mice. From the same patient, we obtain tumor tissue and T cells. This allows the creation of an autologous mouse system, where the components, immune system, tumor, and cell-based therapy, all come from the same source. In doing so, we avoid any complications that would arise from cells coming from multiple individuals.
We are working on validating the autologous mouse system by generating chimeric antigen receptor (CAR) T cells from the patients’ own T cells. These redirected T cells allow for evaluation of the model system, both in terms of how the tumors respond to immunotherapy and how the existing immune system responds to immunotherapy. Results in the animal model are compared to those of patients receiving the same treatment in clinical trials at the University of Pennsylvania.
Preferred Qualifications
Enthusiasm for cancer immunotherapy research
Project Website
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Details:
Preferred Student Year
First-year, Second-Year, Junior, Senior
Academic Term
Fall, Summer
I prefer to have students start during the above term(s).Volunteer
Yes
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Yes
Yes indicates that faculty are open to paying students they engage in their research, regardless of their work-study eligibility.Work Study
Yes
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