Phase I Study of IL13Rα2-Targeting CAR T Cells After Lymphodepletion for Children with Refractory or Recurrent Malignant Brain Tumors
Grant Award Details
Grant Type:
Grant Number:
CLIN2-12153
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Award Value:
$8,401,309
Status:
Active
Grant Application Details
Application Title:
Phase I Study of IL13Rα2-Targeting CAR T Cells After Lymphodepletion for Children with Refractory or Recurrent Malignant Brain Tumors
Public Abstract:
Therapeutic Candidate or Device
Autologous chimeric antigen receptor T cells derived from naive/memory T cells and engineered to target IL13Rα2 on pediatric malignant brain tumors.
Indication
Recurrent/refractory malignant pediatric brain tumors that express the tumor-associated antigen IL13Rα2.
Therapeutic Mechanism
Naive and memory T cells are harvested from patients and reprogrammed to express chimeric antigen receptors for targeted tumor killing. Upon adoptive transfer, the CAR product recognizes and destroys malignant brain tumor cells expressing IL13Rα2. Lymphodepleting chemotherapy is included in this trial to augment the proliferation, persistence, and efficacy of these cells.
Unmet Medical Need
This proposal addresses the critical unmet medical need for effective therapies to treat aggressive pediatric brain tumors, including glioblastoma, medulloblastoma, atypical teratoid/rhabdoid tumor, diffuse midline glioma, and others.
Project Objective
Phase I trial completed and Phase II trial enabled
Major Proposed Activities
Autologous chimeric antigen receptor T cells derived from naive/memory T cells and engineered to target IL13Rα2 on pediatric malignant brain tumors.
Indication
Recurrent/refractory malignant pediatric brain tumors that express the tumor-associated antigen IL13Rα2.
Therapeutic Mechanism
Naive and memory T cells are harvested from patients and reprogrammed to express chimeric antigen receptors for targeted tumor killing. Upon adoptive transfer, the CAR product recognizes and destroys malignant brain tumor cells expressing IL13Rα2. Lymphodepleting chemotherapy is included in this trial to augment the proliferation, persistence, and efficacy of these cells.
Unmet Medical Need
This proposal addresses the critical unmet medical need for effective therapies to treat aggressive pediatric brain tumors, including glioblastoma, medulloblastoma, atypical teratoid/rhabdoid tumor, diffuse midline glioma, and others.
Project Objective
Phase I trial completed and Phase II trial enabled
Major Proposed Activities
- manufacture and release of IL13BBζ-Tn/mem CAR T cells
- evaluate safety and feasibility of intraventricularly-delivered CAR T cells administered after lymphodepletion in pediatric patients
- develop and establish methods and target populations for Phase II clinical trial
Statement of Benefit to California:
This proposal will benefit California residents by developing more effective and less toxic therapies for aggressive pediatric brain tumors. This will result in lives prolonged or saved, fewer missed days of work, and less economic and emotional burden to families and caregivers. Additionally, it will create and support skilled jobs, serve to recruit talent from elsewhere in the country/world, and cement California's leadership in this field.
Publications
- Nat Commun (2023): Antigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting. (PubMed: 37550294)
- Curr Oncol Rep (2023): Cellular Therapy for Children with Central Nervous System Tumors: Mining and Mapping the Correlative Data. (PubMed: 37160547)
- EBioMedicine (2022): Improving CAR-T immunotherapy: Overcoming the challenges of T cell exhaustion. (PubMed: 35301179)
- Cancer Res Commun (2023): Inclusion of 4-1BB Costimulation Enhances Selectivity and Functionality of IL13Ralpha2-Targeted Chimeric Antigen Receptor T Cells. (PubMed: 36968221)
- Nat Med (2024): Locoregional delivery of IL-13Ralpha2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial. (PubMed: 38454126)
- Nat Med (2023): Tumor inflammation-associated neurotoxicity. (PubMed: 37024595)
