# A Novel Adenoviral-Permissive, Immunocompetent Hamster Model to Evaluate Oncolytic Adenoviral Therapy for Glioblastoma

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $454,473

## Abstract

Despite oncolytic adenoviruses emerging as promising new therapeutics for patients with glioblastoma (GBM),
there are no translational mammalian models in an immune competent animal that are permissive to adenoviral
infection and that allow for integration of both the oncolytic and immune effects of these viruses. The overall
objectives of this proposal are to develop and characterize a Golden hamster model of GBM that addresses the
limitations of existing murine models with respect to pre-clinical testing of oncolytic adenoviral therapy. The
central hypothesis is that hamster GBM models will provide reliable pre-clinical data to decipher oncolytic
adenoviral therapeutic mechanisms and to evaluate preclinical strategies for translation to patients. The rationale
for the proposed research is that understanding the interactions between viral oncolysis and the immune system
will uncover mechanisms of therapeutic efficacy, identify which patients might respond best, and reveal new
combinatorial therapeutic approaches. The central hypothesis will be tested in three specific aims: 1) Develop
hamster glioma stem cell (hamGSC) lines that reflect common molecular alteration in human glioma, 2)
Characterize the hamster immune response to oncolytic adenovirus, and 3) Evaluate the effects of
pharmacological manipulation of the immune system on the efficacy of Delta-24-RGD. In Aim 1, CRISPR gene
targeting will be used to create hamGSC lines driven by specific driver alterations to reflect human GBM
molecular subtypes. In Aim 2, the immune response to oncolytic adenovirus will be characterized. Using T-cell
depletions strategies, the contributions of immune effector cells to oncolytic virus efficacy and long-term immune
memory and the impacts of pre-existing exposure to adenovirus will be evaluated. Aim 3 will evaluate the effects
of immune function via either corticosteroids or immune checkpoint inhibitors on oncolytic adenovirus therapeutic
efficacy. Collectively, the studies proposed in this application will result in the development and characterization
of a novel mammalian model for translational evaluation of oncolytic adenovirus in the treatment of GBM. This
contribution is significant because it will overcome many limitations of mouse glioma models and for the first time
provide a platform for pre-clinical studies to evaluate the efficacy and mechanisms of oncolytic adenoviral therapy
against GBM. The proposed research is innovative because this is the first hamster glioma model that is
intracranial, immune competent, and adenoviral replication permissive. This represents a distinct advantage over
traditional murine models, particularly in the setting of evaluating immune-modulating therapies such as oncolytic
adenoviral therapy.

## Key facts

- **NIH application ID:** 10115006
- **Project number:** 5R01CA247970-02
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** FREDERICK F LANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $454,473
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115006

## Citation

> US National Institutes of Health, RePORTER application 10115006, A Novel Adenoviral-Permissive, Immunocompetent Hamster Model to Evaluate Oncolytic Adenoviral Therapy for Glioblastoma (5R01CA247970-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10115006. Licensed CC0.

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