# Off-the-shelf engineered NK cells to treat glioblastoma

> **NIH NIH R43** · MONON BIOVENTURES, LLC · 2022 · $399,314

## Abstract

PROJECT SUMMARY
Glioblastoma (GBM) is the most lethal form of brain cancer and more than 12,000 people are diagnosed with
this disease every year. Current standard of care involved surgery where possible, followed by a combination of
chemotherapy and radiotherapy. Unfortunately, the outcome of treatment remains poor with only 15% of patients
surviving beyond 5 years. Recent advances in immunotherapy, such as CAR-T cell therapy, have been
promising with other cancers but numerous studies have identified several hurdles in applying these methods
effectively to glioblastoma. Particularly, GBM cells have high heterogeneity allowing them to escape immune
detection, and they present an immunosuppressive microenvironment which reduces the efficacy of
immunotherapies. Moreover, the engineered T cells are challenging to source as they elicit a strong graft-vs-
host disease response. Monon Bioventures, in collaboration with Dr. Matosevic at Purdue University, is
developing an immunotherapy that addresses the limitations of previous approaches. We have designed a novel
triple-specific CAR-NK cell capable of overcoming these hurdles through multiple specific mechanisms –
improved tumor infiltration and locally-responsive targeted activity while overcoming multiple mechanisms of
immunosuppression. Additionally, NK cells do not require stringent donor-recipient matching and can be
obtained off-the-shelf. Preliminary studies with the triple-specific CAR-NK cells show efficient killing of GBM cells
in vitro. Further, in vivo studies with GBM xenografted mice show increased tumor infiltration, reduction in tumor
growth and improved survival. Monon Bioventures is bringing this promising therapy from the lab to the clinic.
To achieve this goal, we propose to develop a scalable method to produce the CAR-NK cells using NK cells
sourced from blood and demonstrate the efficacy of the therapeutic in a GBM xenograft model. The following
Specific Aims are planned: Aim 1. Engineer and characterize NK cells isolated from cord blood. This will be
carried out through two sub-tasks: Aim 1 A. Recreate the novel lentiviral vector designed by Dr. Matosevic in a
GMP-capable facility, validating vector production through scalable methods that are consistent with cGMP
standards. Aim 1B. Isolate and transduce NK cells from cord blood; determine transduction efficiency and
characterize functionality of the CAR-NK cells. Aim 2. Demonstrate efficacy of CAR-NK in a patient-derived GBM
xenograft mouse model. This project will generate the results needed for a Type B Pre-IND meeting with the
FDA. With feedback from the FDA, Phase II funding will go to support the IND package necessary to begin the
Phase I trial. Once developed, our novel CAR-NK based therapy has the potential to establish a much-needed
new standard of care for those suffering from GBM and could significantly improve the outcome of the disease.

## Key facts

- **NIH application ID:** 10481503
- **Project number:** 1R43CA271914-01
- **Recipient organization:** MONON BIOVENTURES, LLC
- **Principal Investigator:** Joe Trebley
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $399,314
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10481503

## Citation

> US National Institutes of Health, RePORTER application 10481503, Off-the-shelf engineered NK cells to treat glioblastoma (1R43CA271914-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10481503. Licensed CC0.

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