# Fgl2 neutralizing therapy for inducing tumor specific brain resident immune memory against CNS tumor relapse

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $604,997

## Abstract

Our goal in this application is to test the hypothesis that neutralizing the newly identified immune-suppressive
regulator fibrinogen-like protein 2 (Fgl2) in glioblastoma (GBM) following standard care chemotherapy will trigger
tumor-specific resident memory T cells in the brain (bTrm cells), which allows immunological clearance of
gliomas within the central nervous system and prevention of GBM recurrence. This hypothesis was raised based
on our recently published papers and newly established preliminary data. In brief, we have discovered that Fgl2
is highly expressed in GBM tissues (Yan et al, JNCI, 2015) and can transform low-grade brain tumors to GBM
(Latha et al, JNCI, 2018). Knockout of Fgl2 in tumor cells completely eliminates tumor progression in the brains
of immune-competent mice but not in immune-deficient mice (Yan et al, Nat Commun, 2019). Our unpublished
preliminary data have shown that neutralizing Fgl2 via administering T cells armed with a membrane-anchored
anti-Fgl2 scFv induces bTrm cells that reject intracranial tumor cell challenge directly or after intracranial
transplantation into naïve mice (see preliminary data section); the same mice are unable to reject tumors from
peripheral tissue challenge.
 To test our central hypothesis, the following aims are proposed: Aim 1: Determine how T-aFgl2–
neutralizing T-cell therapy induces bTrm cells in brains; Aim 2: Optimize the T-aFgl2–neutralizing cell
therapy and develop a next-generation T-aFgl2 cell therapy for boosting safety and therapeutic efficacy.
 Impact: This study will yield a therapeutic candidate—an Fgl2-neutralizing cell therapy that may
permanently prevent tumor recurrence—the key deadly cause of GBM patient death. Considering that Fgl2 can
be detected in almost all GBMs, with most having very high levels, this candidate therapeutic will be important.
This study will also further mechanistically elucidate how Fgl2-neutralizing cell therapy induces bTrm cells and
how we can make additional improvements to move this therapy into the next phase. Ultimately, this novel field
will transform the treatment of GBM.

## Key facts

- **NIH application ID:** 10275974
- **Project number:** 1R01NS122857-01
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Amy Beth Heimberger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $604,997
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10275974

## Citation

> US National Institutes of Health, RePORTER application 10275974, Fgl2 neutralizing therapy for inducing tumor specific brain resident immune memory against CNS tumor relapse (1R01NS122857-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10275974. Licensed CC0.

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