# Pilot Project 1: Combination of Viroimmunotherapy and Microbiota Modulation to Treat Gastric Cancer

> **NIH NIH U54** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $64,219

## Abstract

PILOT PROJECT 1: COMBINATION OF VIROIMMUNOTHERAPY AND MICROBIOTA MODULATION TO
TREAT GASTRIC CANCER
PROJECT SUMMARY/ABSTRACT
Gastric cancer is the third leading cause of cancer-related mortality, with a 5-year survival rate of
approximately 20%. The incidence and mortality rates of gastric cancer in the U.S. are of high concern,
especially among non-white populations. Hispanic, black non-Hispanic, and Asian/Pacific Islander populations
have a 40-50% higher risk of gastric cancer than white people, and African Americans are nearly twice as likely
to die of stomach cancer. Virotherapy, as a special case of immunotherapy, is showing promising results for
solid tumors in clinical trials. We developed an oncolytic adenovirus, Delta-24-RGD, which was clinically tested
in a first-in-human phase I clinical trial in patients with recurrent glioblastoma. Clinical trials and preclinical
studies showed that the intratumoral injection of Delta-24-RGD triggered an anti-tumor immune response that
induced complete tumor regression in a small but significant percentage of patients. These clinical data
emphasize the need to develop strategies that will significantly increase the percentage of solid tumors like
gastric cancer sensitive to virotherapy. Recent studies showed that the intestinal microbiota influence the
efficacy of immunotherapy. These clinical data have been supported by rigorously controlled experiments
using gnotobiotic mouse models colonized with one or more specific bacteria, which showed that certain
microbial biomarkers were associated with modulating and enhancing anti-tumor therapies, such as improving
efficacy of immunotherapy. These data suggest that therapeutic interventions aimed at altering the gut
microbiome may influence the final clinical outcome. Here, we hypothesize that oncolytic adenoviruses will
exert an effective anti-cancer effect in gastric cancer, and that the host gut microbiome plays an important role
in modulating the virus-driven anti-tumor response. To test this hypothesis, we propose the following aims:
Aim 1. Characterize the anticancer-potency elicited by armed oncolytic adenovirus in gastric cancer. We will
utilize the Delta-24-RGD platform of replication-competent, tumor-selective adenoviruses, and the next
generation of Delta-24-RGD armed with the immunomodulator OX40L, Delta-24-RGDOX. Aim 2. Examine the
role of gut microbial communities in modulating the efficacy of the viroimmunotherapy. We will assess the anti-
cancer effect of the oncolytic therapy in relation to different bacterial signatures. This project should yield new
information about the potential use of oncolytic adenoviruses as therapy for gastric cancer and will open
avenues to include intestinal microbiota as a potential treatment modifier, by maximizing the synergy between
laboratories at the University of Puerto Rico (UPR) and M.D. Anderson Cancer Center (MDACC). Our pilot
project is aligned with the Infection-Driven Malignancies Program for Advan...

## Key facts

- **NIH application ID:** 10249301
- **Project number:** 5U54CA096300-18
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** Candelaria Gomez-Manzano
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $64,219
- **Award type:** 5
- **Project period:** 2002-08-16 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249301

## Citation

> US National Institutes of Health, RePORTER application 10249301, Pilot Project 1: Combination of Viroimmunotherapy and Microbiota Modulation to Treat Gastric Cancer (5U54CA096300-18). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10249301. Licensed CC0.

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