# Project 1: Combine Viro-Immunotherapy and Natural Killer Cells for the Treatment of Gliomas

> **NIH NIH P50** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $339,949

## Abstract

SUMMARY: PROJECT 1
Through our pioneering work with the anti-glioma oncolytic virus Delta-24-RGD, it is now recognized that
oncolytic viruses are potent anti-cancer immunotherapeutic agents, acting not only by direct oncolysis but also
by inducing an anti-glioma immune response. This paradigm-shifting concept implies that oncolytic viruses,
including Delta-24-RGD, alter the immune tumor microenvironment (TME) and may therefore induce synergistic
effects when combined with other immunotherapy strategies. However, there is a significant gap in knowledge
regarding the ideal agent to use in combination with Delta-24-RGD. In this content, we have recently engineered
natural killer (NK) cells (called eCB-NK-TF-/GC- cells) for glioblastoma (GBM) which are resistant to tumor- and
corticosteroid-induced immunosuppression by inactivation of TGFβ-Receptor 2 and the glucocorticoid receptor
2, respectively. In our current SPORE, we initiated a dose escalation/window-of-opportunity clinical trial of eCB-
NK-TF-/GC- cells as a single agent in patients with recurrent GBM. In parallel pilot experiments exploring the
interaction of Delta-24-RGD and NK cells, we have shown that treatment with Delta-24-RGD increased the
recruitment, anti-cancer activity, survival, and memory of endogenous NK cells. Importantly, treatment with
Delta-24-RGD followed by eCB-NK-TF-/GC- extended the survival of glioma-bearing mice compared with
controls. Based on these preliminary data, we hypothesize that Delta-24-RGD treatment will actively contribute
to enhancing the activity and memory of off-the-shelf eCB-NK-TF-/GC- cells resulting in strong anti-tumor activity
without undue toxicity in patients with GBM. To test this hypothesis we will: Leverage the post-treatment
biological specimens obtained from the window-of-opportunity arm of our ongoing Phase 1 clinical trial to
evaluate the fate of eCB-NK-TF-/GC- cells as a single agent and to determine the associated immune changes
in the TME of patients with recurrent GBM (Aim 1); Explore the combination of Delta-24-RGD and eCB-NK-TF-
/GC- cells in a variety of preclinical animal models to evaluate the impact on the TME in GBM (Aim 2); And
execute a phase I clinical trial with a window-of-opportunity arm of intratumorally administered Delta-24-RGD in
combination with eCB-NK-TF-/GC- cells in patients with recurrent GBM (Aim 3). The samples obtained from the
combination trial (Aim 3) will be compared with the samples from the single agent trial (Aim1) to assess the ability
of Delta-24-RGD to alter the TME and enhance the activity of eCB-NK-TF-/GC- cells in patients. Our SPORE
team has a consistent track record of translating therapies from the laboratory to the clinical setting, and this
project is the next critical step in achieving our long-term goal of making viro-immunotherapy a standard
treatment for malignant glioma.

## Key facts

- **NIH application ID:** 10847567
- **Project number:** 2P50CA127001-16
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Juan Fueyo
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $339,949
- **Award type:** 2
- **Project period:** 2008-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10847567

## Citation

> US National Institutes of Health, RePORTER application 10847567, Project 1: Combine Viro-Immunotherapy and Natural Killer Cells for the Treatment of Gliomas (2P50CA127001-16). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10847567. Licensed CC0.

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