the kyra fund
Project Rose
Kyra’s Hebrew name is Shoshana, which translates to “rose.” Kyra’s Hebrew name memorializes her paternal great grandmother, Rose. Additionally, Kyra loved drinking a crisp glass of rosé on a rooftop in the summer heat, allowing this project’s name to have two unique meanings that honor Kyra.
This project, formally titled Combination strategy integrating γδ T cell and cytotoxic therapy for glioblastoma, is taking place at the Preston Robert Tisch Brain Tumor Center at Duke. The work is supported by the Glioblastoma Research Organization through a $100,000 grant.
About The Project
Glioblastoma is the most aggressive type of brain cancer in adults and remains extremely difficult to treat. Even after surgery, radiation, and chemotherapy, most patients experience tumor recurrence, and current treatments provide limited benefit. As a new treatment approach, we have developed a novel tumor cell-targeted therapy called an antibody-toxin conjugate (ATC), which links an antibody, a protein that recognizes tumor cells, to a toxin that kills them. In an early-stage clinical trial of patients with progressive glioblastoma, patients treated with ATC lived for an average of approximately eight months. We hypothesized that immune cells within the tumor that limit antitumor responses may reduce the effectiveness of the ATC alone. We therefore combined ATC with an antibody called αCD40, which activates immune cells and promotes their ability to respond against cancer. In a second early-stage clinical trial of patients with progressive glioblastoma, those treated with ATC plus αCD40 lived for an average of approximately 13 months. Together, these findings support further investigation of treatment strategies that simultaneously target tumor cells and stimulate the immune system.
Importantly, we found that patients who lived longer after treatment with ATC or ATC plus αCD40 had higher levels of a unique type of immune cell, called gamma delta (γδ) T cells, in their blood and tumors. Unlike conventional T cells, γδ T cells can recognize and kill cancer cells without requiring the same type of tumor recognition used by conventional T cells. We hypothesize that γδ T cells may contribute to stronger antitumor responses and longer survival in a subset of patients with glioblastoma. In Project Rose, we will investigate how γδ T cells contribute to treatment responses in patients receiving ATC or ATC plus αCD40. We will analyze blood samples collected before and after treatment to identify differences in γδ T cells between patients who experience longer and shorter survival. We will also isolate γδ T cells from long-term survivors, expand them in the laboratory, and test their ability to recognize and kill glioblastoma cells. By defining how γδ T cells contribute to tumor killing, this research may identify new opportunities to enhance ATC-based therapy and inform the development of combination treatments that could improve survival and quality of life for patients with glioblastoma.
Dr. Vidya Chandramohan
Ph.D., M.B.A.
Associate Professor in Neurosurgery
Dr. Vidya Chandramohan is an Associate Professor of Pathology and Neurosurgery at Duke University Medical Center. She earned her Ph.D. in Biochemistry with a focus on Cell and Molecular Biology from Boston University and completed postdoctoral training at Duke University, where she developed an antibody-toxin conjugate (ATC) targeting EGFRwt and EGFRvIII for the treatment of glioblastoma. ATC is currently being evaluated in clinical trials for patients with glioblastoma.
Dr. Chandramohan’s research focuses on developing strategies to enhance the effectiveness of ATC and ATC-based combination therapies by activating the tumor immune microenvironment and identifying biomarkers that predict treatment response. Her laboratory also uses single-cell and multi-omics approaches to characterize tumor and immune cells in brain tumors and define mechanisms of therapeutic response and resistance.
