Phase 1 Study of Autologous E-SYNC T Cells in Adult Participants with EGFRvIII+ Glioblastoma
Grant Award Details
Grant Type:
Grant Number:
CLIN2-15562
Investigator(s):
Disease Focus:
Award Value:
$10,927,618
Status:
Active
Grant Application Details
Application Title:
Phase 1 Study of Autologous E-SYNC T Cells in Adult Participants with EGFRvIII+ Glioblastoma
Public Abstract:
Therapeutic Candidate or Device
Human T cells transduced with a lentiviral vector encoding anti-EGFRvIII synNotch-primed anti-EphA2/IL-13Rα2 chimeric antigen receptor.
Indication
Patients with MGMT unmethylated newly diagnosed GBM (Cohort 1), and patients for whom re-resection of recurrent GBM (Cohort 2).
Therapeutic Mechanism
In our proposed system, the first antigen EGFRvIII, which is expressed exclusively but heterogeneously on glioblastoma cells, primes the T cells to induce expression of a CARthat recognizes EphA2 and IL-13Rα2, thereby eradicating glioblastoma cells expressing either EphA2 or IL-13α2. Efficacy was long-lasting and superior to conventional CARTcells. 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 andchemotherapy, prognosis remains poor with a 100% recurrence rate and median overall survival of approximately 20 months.
Project Objective
Phase 1 trial completed
Major Proposed Activities
Human T cells transduced with a lentiviral vector encoding anti-EGFRvIII synNotch-primed anti-EphA2/IL-13Rα2 chimeric antigen receptor.
Indication
Patients with MGMT unmethylated newly diagnosed GBM (Cohort 1), and patients for whom re-resection of recurrent GBM (Cohort 2).
Therapeutic Mechanism
In our proposed system, the first antigen EGFRvIII, which is expressed exclusively but heterogeneously on glioblastoma cells, primes the T cells to induce expression of a CARthat recognizes EphA2 and IL-13Rα2, thereby eradicating glioblastoma cells expressing either EphA2 or IL-13α2. Efficacy was long-lasting and superior to conventional CARTcells. 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 andchemotherapy, prognosis remains poor with a 100% recurrence rate and median overall survival of approximately 20 months.
Project Objective
Phase 1 trial completed
Major Proposed Activities
- We will evaluate the safety of IV-infused E-SYNC T cells in patients with MGMT unmethylated newly diagnosed GBM (Cohort 1).
- We will evaluate the infiltration and priming of the IV-infused E-SYNC T cells in the resected tumor tissue (Cohort 2)
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 healthcare clinicians work in partnership to translate laboratory findings into new or improved forms of clinical therapy for patients in California.