Journal article
Phase 1 dose escalation trial of vv-DD-hIL-2-RG-1 (vaccinia virus double deleted) administration by intratumoral injection for metastatic gastrointestinal tumors: The regional immuno-oncology trial - 3 (RIOT-3) protocol
Surgical oncology insight, v 2(3), 100185
01 Sep 2025
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Current treatments for metastatic gastrointestinal malignancies have poor outcomes, necessitating a novel approach to treatment. Oncolytic therapy with vaccinia viruses has previously shown promising results in terms of safety and anti-tumor efficacy. In addition to direct viral cytotoxic effects, oncolytic therapy has the potential to stimulate adaptive immunity against infected tumor cells by altering the tumor microenvironment. The immunostimulatory effects of oncolytic vaccinia vectors have been maximized through the use of recombinant vectors encoding interleukin-2 (IL-2), a potent cytokine that signals T cell activity and proliferation. This report details the use of a novel oncolytic vaccinia vector-- vvDD-hIL-2-RG-1—which encodes a rigid peptide-linked, membrane-bound form of IL-2, designed to maximize the local immunomodulatory activity following intra-tumoral injection.
RIOT-3 is a phase 1, open-label, single-dose, dose-escalation trial investigating intratumoral injection of vvDD-hIL-2-RG-1. Up to 18 participants with metastatic gastrointestinal cancer who have failed systemic chemotherapy or immunotherapy will be enrolled. The primary study objective is to determine the safety and maximal tolerated and feasible doses for intratumoral injection via a 3 + 3 dose escalation design. Secondary objectives include quantifying viral replication, pharmacokinetics, and immune response to vvDD-hIL-2-RG-1 intratumoral injection, as well as efficacy assessment by RECIST criteria.
Previous preclinical data in a murine model have demonstrated that IL-2-bound vaccinia oncolytic virus is safe and exerts dose-dependent anti-tumor activity. RIOT-3 will explore the application of this novel oncolytic viral approach in patients with advanced gastrointestinal malignancies who have failed conventional therapies. The trial is registered at ClinicalTrials.gov; NCT07001592 (registered May 6th, 2025).
Metrics
2 Record Views
Details
- Title
- Phase 1 dose escalation trial of vv-DD-hIL-2-RG-1 (vaccinia virus double deleted) administration by intratumoral injection for metastatic gastrointestinal tumors: The regional immuno-oncology trial - 3 (RIOT-3) protocol
- Creators
- Brett M. Szeligo - Allegheny Health NetworkShannon Altpeter - Allegheny Health NetworkCatherine Lewis - Allegheny Health NetworkAlbert D. Donnenberg - Allegheny Health NetworkChristopher Sherry - Allegheny Health NetworkVera S. Donnenberg - University of PittsburghPaige Mirsky - Allegheny Health NetworkNeda Dadgar - Allegheny Health NetworkAli Zaidi - Allegheny Health NetworkNathan Bahary - Allegheny Health NetworkZuqiang Liu - Allegheny Health NetworkDavid L. Bartlett - Allegheny Health NetworkPatrick L. Wagner (Corresponding Author) - Allegheny Health Network
- Publication Details
- Surgical oncology insight, v 2(3), 100185
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Surgery; General Internal Medicine
- Web of Science ID
- WOS:001620435000019
- Scopus ID
- 2-s2.0-105014284347
- Other Identifier
- 991022197300504721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
Source: SDGs in the Output
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology
- Surgery