# Optimizing CAR T therapy via metabolic engineering for thetreatment of GBM

> **NIH NIH R21** · MAYO CLINIC  JACKSONVILLE · 2024 · $203,187

## Abstract

PROJECT SUMMARY AND ABSTRACT
Significance: Glioblastoma (GBM) is an extremely devastating disease with reported median survivals ranging
from 13 to 73 months and 5-year survivals of less than 20% in children and about 15 months with less than 5%
5-year survival rate for adult patients. Cancer immunotherapy using chimeric antigen receptor (CAR) modified T
cells is a promising treatment, however its efficacy in GBM has been limited.
Hypothesis: We hypothesize that the fierce competition for nutrients within the tumor microenvironment,
especially glucose, between tumor cells and the immune system, imposes an abundant metabolic pressure to
CAR T cells dampening their effector function and intratumoral infiltration, expansion, and persistence.
Objective: The goal of this study is to validate a new strategy to overcome this metabolic imbalance and provide
a competitive advantage to CAR T cells over tumor cells. We propose to improve CAR T cell therapy by
enhancing metabolic fitness to outcompete GBM cells for nutrients like glucose.
Methods: Our approach will be to directly target the first step of glucose metabolism (i.e., uptake) by permanent
overexpression of GLUT1 or GLUT3 and generating the following CAR T cells: CD70CAR.G1 and CD70CAR.G3.
The murine model of glioma KR158B, derived from Nf1;Trp53 mutant mouse, that we engineered to express
CD70 as well as CD70 expressing human GBM patient-derived cell lines will be used for the following aims:
Specific Aims
 1. Investigate the phenotypic and functional characteristics of metabolically modified CD70CAR T cells,
 2. Evaluate in vivo the metabolic TME of animals treated with CD70CAR.G1 or CD70CAR.G3,
 3. Examine the safety and anti-tumor efficacy of CD70CAR.G1 or CD70CAR.G3.

## Key facts

- **NIH application ID:** 11239302
- **Project number:** 7R21CA282979-03
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** Loic Pierre Deleyrolle
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $203,187
- **Award type:** 7
- **Project period:** 2023-07-05 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11239302

## Citation

> US National Institutes of Health, RePORTER application 11239302, Optimizing CAR T therapy via metabolic engineering for thetreatment of GBM (7R21CA282979-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11239302. Licensed CC0.

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