Development of novel synNotch CART cell therapy in patients with recurrent EGFRvIII+ glioblastoma
Grant Award Details
Grant Type:
Grant Number:
TRAN1-12245
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$525,000
Status:
Closed
Grant Application Details
Application Title:
Development of novel synNotch CART cell therapy in patients with recurrent EGFRvIII+ glioblastoma
Public Abstract:
Translational Candidate
Human T cells transduced with a lentiviral vector encoding anti-EGFRvIII synNotch-primed anti-EphA2/IL-13Rα2 chimeric antigen receptor.
Area of Impact
Glioblastoma is the most common malignant brain tumor, affecting approximately 3 out of 100,000 people/year in the USA with extremely poor prognosis.
Mechanism of Action
In our proposed system, the first antigen EGFRvIII, which is expressed exclusively but heterogenenously on glioblastoma cells, primes the T cells to induce expression of a CAR that recognizes EphA2 and IL-13Rα2, thereby eradicating glioblastoma cells expressing either EphA2 or IL-13α2. Efficacy was long-lasting and superior to conventional CART cells. The superb efficacy of these synNotch-CART cells was associated with excellent persistence (>100 days in vivo) and T stem memory cell phenotype.
Unmet Medical Need
Glioblastoma is the most common malignant primary brain tumor, affecting approximately 3 out of 100,000 individuals/year in the USA. Despite surgical resection, radiation and chemotherapy, prognosis remains poor with a 100% recurrence rate and median overall survival of approximately 20 months.
Project Objective
Successful submission of a Pre-IND application
Major Proposed Activities
Human T cells transduced with a lentiviral vector encoding anti-EGFRvIII synNotch-primed anti-EphA2/IL-13Rα2 chimeric antigen receptor.
Area of Impact
Glioblastoma is the most common malignant brain tumor, affecting approximately 3 out of 100,000 people/year in the USA with extremely poor prognosis.
Mechanism of Action
In our proposed system, the first antigen EGFRvIII, which is expressed exclusively but heterogenenously on glioblastoma cells, primes the T cells to induce expression of a CAR that recognizes EphA2 and IL-13Rα2, thereby eradicating glioblastoma cells expressing either EphA2 or IL-13α2. Efficacy was long-lasting and superior to conventional CART cells. The superb efficacy of these synNotch-CART cells was associated with excellent persistence (>100 days in vivo) and T stem memory cell phenotype.
Unmet Medical Need
Glioblastoma is the most common malignant primary brain tumor, affecting approximately 3 out of 100,000 individuals/year in the USA. Despite surgical resection, radiation and chemotherapy, prognosis remains poor with a 100% recurrence rate and median overall survival of approximately 20 months.
Project Objective
Successful submission of a Pre-IND application
Major Proposed Activities
- Process development for manufacturing of EGFRvIII-primed EphA2/IL-13Rα2 CART cells
- In vivo (rodent) studies to determine preclinical efficacy and safety of the proposed cell products
- Development of the clinical trial protocol, consent form and clinical standard operating procedures (SOPs)
Statement of Benefit to California:
Because the current California's population is nearly 40 million, approximately 1,200 people are likely to be diagnosed with this devastating disease every year. The Brain Tumor Center within the Department of Neurosurgery at UCSF is one of the most established brain tumor research and treatment centers in the world. Our scientists and health care clinicians work in partnership to translate laboratory findings into new or improved forms of clinical therapy for patients in California.