# Oncolytic Adenoviruses for Glioma Therapy

> **NIH NIH P50** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $327,149

## Abstract

SUMMARY: PROJECT 1
To improve the notoriously poor outcome of patients with malignant gliomas, we developed a novel oncolytic
adenovirus, Delta-24-RGD, that selectively replicates in and destroys glioma cells. This virus was tested in a
first-in-human Phase I clinical trial in patients with recurrent malignant gliomas (NCT00805376), in which
dramatic complete (>95% tumor reduction) and durable (>3 years) responses were observed in 12% of patients.
Data from this trial contributed to the groundbreaking paradigm shift demonstrating that the Delta-24-RGD
oncolytic virus is a form of immunotherapy. Specifically, analyses of clinical responses and post treatment
surgical specimens demonstrated that the oncolytic effect of Delta-24-RGD is followed by an anti-tumor cytotoxic
T cell immune response that is capable of resulting in complete tumor regression in a small but significant
percentage of patients. These clinical data emphasize the urgent need to amplify the anti-tumor immune
response as a means of enhancing the efficacy of Delta-24-RGD. To this end, in this proposal we pursue two
convergent approaches whose foundations rest on the concept that immune responses to tumors are mediated
by 1) immune checkpoints molecules that attenuate immune responses and against which FDA-approved
inhibitors are available, and 2) immune costimulatory molecules which activate immune responses and are ideal
to “arm” Delta-24-RGD. In our first approach, we combine Delta-24-RGD with the immune checkpoint inhibitor
Pembrolizumab (MERCK), that is directed against the cell surface checkpoint receptor PD-1. We take advantage
of the pretreatment biopsy specimens obtained from an ongoing Phase I/II clinical trial of this combination in
patients with recurrent gliomas (the CAPTIVE trial, NCT02798406), to not only assess the safety and efficacy of
this combination, but also to assess biomarkers for response (Aim 1). In our second approach, we develop and
test next-generation Delta-24-RGD viruses that are armed with the cDNA of the ligands of immune co-stimulatory
receptors (OX40L, GITRL, 4-1BB). We have already constructed and fully characterized the anti-glioma effects
of Delta-24-RGDOX, which carries OX40L, and our data show that Delta-24-RGDOX more efficiently eradicates
gliomas compared with Delta-24-RGD in immunocompetent animal models. Therefore, in Aim 2 of this proposal
we assess the safety and biological effects of Delta-24-RGDOX on patient tumors in a unique treat-resect-treat
clinical trial. Lastly, in Aim 3 we characterize the anti-glioma effects of additional next generation viruses Delta-
24-GREAT (which contains GITRL) and Delta-24-ACT (which contains 4-1BBL) alone and in combination with
Delta-24-RGD, to define potential synergy of these viruses. If successful, Project 1 will usher in a new age of
oncolytic viral therapies for the treatment of malignant gliomas, for which there is currently no effective treatment.

## Key facts

- **NIH application ID:** 10005138
- **Project number:** 5P50CA127001-12
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** FREDERICK F LANG
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $327,149
- **Award type:** 5
- **Project period:** 2008-09-01 → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10005138

## Citation

> US National Institutes of Health, RePORTER application 10005138, Oncolytic Adenoviruses for Glioma Therapy (5P50CA127001-12). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10005138. Licensed CC0.

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