Neuro-Immuno-Oncology Fellowship & CAR T Research Expansion

Project Overview
In June 2022, ChadTough Defeat DIPG extended its original support of Stanford University’s Neuro-Immuno-Oncology (NIO) Fellowship Program with a three-year expansion grant, recognizing both the early success of the fellowship and the urgent need to deepen laboratory-based discovery alongside clinical innovation.
This expanded funding was designed to support: One neuro-immuno-oncology clinical fellow, and Two postdoctoral research fellows focused on CAR T cell therapy for Diffuse Intrinsic Pontine Glioma (DIPG) and other diffuse midline gliomas (DMG).
The goal of this extension was twofold: to continue training clinician-scientists capable of safely delivering immunotherapies for CNS tumors, and to accelerate laboratory research that could refine, optimize, and expand the effectiveness of GD2-targeted CAR T cell therapy. Any funds not required for fellowship support were allocated toward research efforts advancing the understanding and treatment of DIPG.

Program Impact
This expanded grant significantly strengthened the bridge between bedside care and bench science, enabling real-time learning from patients treated on the GD2-CAR T clinical trial to directly inform laboratory discovery—and vice versa. As documented in annual progress reports, this support helped:
1. Sustain the Neuro-Immuno-Oncology Fellowship during a critical growth phase
2. Support postdoctoral scientists embedded in the Monje Lab working on CAR T cell persistence, resistance, and toxicity
3. Generate one of the largest datasets in the world examining immune responses in the cerebrospinal fluid of patients receiving CAR T therapy for CNS tumors
4. Inform multiple protocol refinements that advanced the trial toward dose expansion and Phase II readiness

Clinical & Research Highlights
Advancing CAR T Therapy for DIPG and DMG
The expanded funding coincided with rapid evolution of the GD2-CAR T clinical trial, including:
1. Identification of safer and more effective dosing strategies using intracerebroventricular (ICV) delivery
2. Improved understanding of tumor inflammation-associated neurotoxicity (TIAN) and how to manage it clinically
3. Entry into dose-expansion phases following the establishment of a recommended Phase II dose, route, and schedule
Postdoctoral Research Contributions
Two postdoctoral fellows supported by this grant played critical roles in:
1. Single-cell and single-nucleus RNA sequencing of patient CSF and tumor tissue
2. Identifying immune and neural signaling pathways associated with response or resistance to CAR T therapy
3. Discovering actionable mechanisms—such as myeloid cell signaling and thrombospondin pathways—that may be targeted to enhance CAR T efficacy in future trials
These findings are now informing the next generation of CAR T trial designs and combinatorial strategies.

Fellowship Continuity & Leadership Development
The extension grant ensured continuity of the Neuro-Immuno-Oncology Fellowship during a period of rapid clinical and scientific advancement. Graduates of the program have gone on to faculty-level roles where they continue to:
1. Care for pediatric and adult patients receiving CAR T therapy
2. Lead clinical trial efforts
3. Publish high-impact research shaping the national approach to immunotherapy for CNS tumors

Looking Ahead
The June 2022 expansion grant positioned the NIO Fellowship and Monje Lab to move beyond proof-of-concept and into optimization, scalability, and national impact. By integrating advanced clinical training with deep laboratory investigation, this project continues to accelerate progress toward safer, more effective immunotherapies for children and young adults diagnosed with DIPG and DMG—diseases that urgently need new treatment options.