Name:
Institution:
Type:
PI
Grant Award Details
Phase I Study of Chimeric Antigen Receptor Engineered Central Memory T cells for the Treatment of Malignant Glioma
Grant Type:
Grant Number:
CLIN2-10248
Project Objective:
Complete a Phase 1 clinical trial for malignant Glioma with autologous Chimeric Antigen Receptor engineered central memory T cells (CAR-Tcm).
Investigator:
Disease Focus:
Brain Cancer
Cancer
Solid Tumors
Human Stem Cell Use:
Adult Stem Cell
Award Value:
$12,753,854
Status:
Active
Grant Application Details
Application Title:
- Phase I Study of Chimeric Antigen Receptor Engineered Central Memory T cells for the Treatment of Malignant Glioma
Public Abstract:
Therapeutic Candidate or Device
A promising immunotherapy utilizing a patient’s memory T cells engineered to express chimeric antigen receptors for targeted tumor killing.
Indication
Malignant glioma (WHO III and IV), including glioblastoma (WHO IV), that express the tumor-associated antigen IL-13 receptor alpha 2 (IL13Rα2).
Therapeutic Mechanism
A promising immunotherapy utilizing a patient’s memory T cells genetically engineered to express chimeric antigen receptors for targeted tumor killing. Upon adoptive transfer the CAR T cell product specifically recognizes and diretly destroys malignant glioma cell expressing IL13Rα2.
Unmet Medical Need
This proposal seeks to address the unmet medical need for more effective therapy against malignant glioma by engineering de novo antitumor immunity using patient-specific chimeric antigen receptor (CAR)-modified T cells.
Project Objective
Phase I trial completed
Major Proposed Activities
- Manufacture and clinically evaluate intraventricular versus dual intraventricular and intratumoral delivery of CAR T cells
- Evaluate safety, feasibility and preliminary evidence of efficacy across all routes of administration.
- Develop and establish reagents and methods for a Phase II clinical trial
Statement of Benefit to California:
This proposal aims to benefit the citizens of California by developing a more effective therapy against glioblastoma, one of the least curable human cancers. Further, this project will produce economic benefits through the creation and maintenance of skilled jobs, along with the purchasing of equipment and supplies from in-state companies. This project will also yield long-reaching benefit by establishing California as a leader in biomedical research both nationally and internationally.
Publications
- PLoS Comput Biol (2022) Dose-dependent thresholds of dexamethasone destabilize CAR T-cell treatment efficacy. (PubMed: 35081104)
- Neuro Oncol (2022) Off-the-shelf, steroid-resistant, IL13Ralpha2-specific CAR T cells for treatment of glioblastoma. (PubMed: 35100373)
- Neoplasia (2022) Spatial organization of heterogeneous immunotherapy target antigen expression in high-grade glioma. (PubMed: 35550513)
- Neurooncol Adv (2021) Repeatability of tumor perfusion kinetics from dynamic contrast-enhanced MRI in glioblastoma. (PubMed: 34988454)
- Front Immunol (2021) Vitamin C, From Supplement to Treatment: A Re-Emerging Adjunct for Cancer Immunotherapy? (PubMed: 34899716)
- Cancer Discov (2021) IFNgamma Is Critical for CAR T Cell-Mediated Myeloid Activation and Induction of Endogenous Immunity. (PubMed: 33837065)
- Cancer Immunol Res (2021) Mitochondria as Playmakers of CAR T-cell Fate and Longevity. (PubMed: 34344697)
- J Immunother Cancer (2021) Deep immune profiling reveals targetable mechanisms of immune evasion in immune checkpoint inhibitor-refractory glioblastoma. (PubMed: 34083417)
- Cancer Discov (2021) CRISPR Screening of CAR T Cells and Cancer Stem Cells Reveals Critical Dependencies for Cell-Based Therapies. (PubMed: 33328215)
- JAMA Oncol (2020) Systemic Anti-PD-1 Immunotherapy Results in PD-1 Blockade on T Cells in the Cerebrospinal Fluid. (PubMed: 33030521)
