# Targeting and Delivering CAR-Ts in Glioblastoma

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $169,106

## Abstract

Project Abstract
The remarkable clinical activity of adoptively transferred T cells redirected with a chimeric antigen receptor
(CAR) specific for the CD19 antigen and encoding co-stimulatory endodomains may change the conventional
treatment of B-cell malignancies in the near future. The development of CAR-T cell-based strategies to treat
patients with glioblastoma (GBM) remains challenging because this tumor shows heterogeneous expression of
targetable tumor-associated antigens, contains stem-cell-like cells that are not usually mirrored by human GBM
cell lines used in preclinical models and shapes pro-tumor and immune suppressive environment. In addition,
the delivery of CAR-Ts in GBM requires novel approaches to ensure that T cells reach and stay within the
tumor environment. We have identified chondroitin sulphate proteoglycan 4 (CSPG4) as highly relevant GBM-
associated antigen for targeted immunotherapy since it is highly and strongly overexpressed in over 68% of
primary GBM samples and not in normal brain. CSPG4 is highly expressed by human stem-cell like GBM cells
such as GBM-derived neurospheres (GBM-NS), and its expression is induced by TNFα released by
inflammatory cells surrounding the tumor. Our data indicate that CSPG4.CAR-Ts can control the growth of
GBM-NS in vitro and in vivo indicating that this strategy may have significant clinical impact. However,
although effective, CSPG4.CAR-Ts do not consistently eradicate GBM-NS. It is our main hypothesis that to
eradicate GBM-NS we need further engineering of CSPG4.CAR-Ts to overcome checkpoint inhibition. We
have also devised an injectable hydrogel that may ensure gradual and longer release of CAR-Ts injected
intratumor. Information generated by the proposal will be instrumental to design the optimal CAR-Ts to
eradicate GBM.

## Key facts

- **NIH application ID:** 9886209
- **Project number:** 5R21CA229938-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Gianpietro Dotti
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $169,106
- **Award type:** 5
- **Project period:** 2019-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9886209

## Citation

> US National Institutes of Health, RePORTER application 9886209, Targeting and Delivering CAR-Ts in Glioblastoma (5R21CA229938-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9886209. Licensed CC0.

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