# Usurping TIGIT and CD73 activities with responsive, genetically-engineered NK cells as immunotherapy for glioblastoma

> **NIH NIH R21** · PURDUE UNIVERSITY · 2022 · $207,796

## Abstract

SUMMARY
 Glioblastoma (GBM) is an extremely aggressive brain cancer, with fewer than 5% of patients surviving to
5 years after diagnosis. The GBM microenvironment fuels its pathogenesis through the expression of CD155,
which drives inhibition of NK cell effector functions via its ligand TIGIT, and the hypoxia-driven generation of
adenosine from ectoenzyme CD73. Adenosine, in turns, impairs the anti-tumor function of natural killer (NK)
cells. As a result, GBM immunotherapies with adoptively-transferred NK cells can be subject to severe
immunosuppression. In order to improve the treatment of GBM, this proposal describes the development of a
novel immunotherapy with NK cells engineered to co-target, in a responsive manner, the inhibitory functions of
TIGIT and CD73. We propose to do so by engaging synthetic notch signaling to usurp TIGIT binding on NK cells
and trigger the local release of CD73 antibody fragments. We will characterize the anti-tumor function and GBM
infiltration of these cells in orthotopic GBM xenografts and make a case for the use of these allogeneic
engineered cells as a safe, powerful immunotherapeutic modality. The highly translational project proposes to
develop curative new immunotherapies for GBM which have the potential to be be translated into effective clinical
treatments in humans.

## Key facts

- **NIH application ID:** 10318207
- **Project number:** 5R21CA256413-02
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Sandro Matosevic
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $207,796
- **Award type:** 5
- **Project period:** 2020-12-11 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10318207

## Citation

> US National Institutes of Health, RePORTER application 10318207, Usurping TIGIT and CD73 activities with responsive, genetically-engineered NK cells as immunotherapy for glioblastoma (5R21CA256413-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10318207. Licensed CC0.

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