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 Advancing Careers and Translational Sciences (IMPACT), in that it will allow us to generate preliminary data with potential to be translated into a full project to address a public health problem among the Hispanic population.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZCA1)
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University of Texas MD Anderson Cancer Center
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Yan, Fangrong; Zhu, Huihong; Liu, Junlin et al. (2018) Design and inference for 3-stage bioequivalence testing with serial sampling data. Pharm Stat 17:458-476
Juan-Rivera, Maylein C; Martínez-Ferrer, Magaly (2018) Integrin Inhibitors in Prostate Cancer. Cancers (Basel) 10:
Gonzalez-Mercado, Velda J; Fridley, Brooke L; Saligan, Leorey N (2018) Sestrin family of genes and their role in cancer-related fatigue. Support Care Cancer 26:2071-2074
Villar-Prados, Alejandro; Wu, Sherry Y; Court, Karem A et al. (2018) Predicting novel therapies and targets: Regulation of Notch3 by the bromodomain protein BRD4. Mol Cancer Ther :
Allen, Julie K; Armaiz-Pena, Guillermo N; Nagaraja, Archana S et al. (2018) Sustained Adrenergic Signaling Promotes Intratumoral Innervation through BDNF Induction. Cancer Res 78:3233-3242
Marqués-Lespier, Juan M; Soto-Salgado, Marievelisse; González-Pons, María et al. (2018) Prevalence of Synchronous Oligopolyposis in Incident Colorectal Cancer: A Population-Based Study. P R Health Sci J 37:39-45
Choi, Sangbum; Kang, Sangwook; Huang, Xuelin (2018) Smoothed quantile regression analysis of competing risks. Biom J 60:934-946
González-Pons, María; Soto-Salgado, Marievelisse; Sevilla, Javier et al. (2018) Seroprevalence of Helicobacter pylori in Hispanics living in Puerto Rico: A population-based study. Helicobacter 23:
Monroig-Bosque, Paloma Del C; Shah, Maitri Y; Fu, Xiao et al. (2018) OncomiR-10b hijacks the small molecule inhibitor linifanib in human cancers. Sci Rep 8:13106
Thapa, Bibek; Diaz-Diestra, Daysi; Santiago-Medina, Carlene et al. (2018) T1- and T2-weighted Magnetic Resonance Dual Contrast by Single Core Truncated Cubic Iron Oxide Nanoparticles with Abrupt Cellular Internalization and Immune Evasion. ACS Appl Bio Mater 1:79-89

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