Review our latest RIOT Program research publications, presentations, and information.
Regional Immuno-Oncology Trial Program (RIOT)
About the Regional Immuno-Oncology Trial Program (RIOT)
The AHN RIOT Program at AHN brings the latest in cancer immunotherapy research and treatment directly to our patients. The RIOT program aims to find better ways to treat cancer, particularly metastatic cancer (cancer that has spread), by boosting the immune system's ability to attack cancer cells.
Regional immuno-oncology is an innovative approach for treating metastatic cancers, especially those that have spread in peritoneal and pleural cavities of the abdomen and in the liver. AHN’s RIOT Program is focused on using immune systems in the fight against cancer and modifying them to work against the disease while minimizing the negative effects of standard immunotherapy spreading through the body. Instead of giving treatments that affect the whole body (like chemotherapy), the RIOT program focuses on delivering treatments directly to the area where the cancer is. This could mean injecting drugs directly into a tumor, or into the chest or abdominal cavity where cancer has spread. The goal is to minimize side effects and maximize the treatment's impact on the cancer.
Instead of using standard immunotherapy, this program tests different types of immunotherapy, frequently and in specific areas of the body, for patients with cancer that has spread (metastatic). The program's studies (called RIOT) are organized by how the treatment is given:
- RIOT 1: RIOT 1 is completed and during the trial, it effectively delivered a toll-like receptor agonist directly into tumors.
- RIOT 2: Delivers a monoclonal antibody drug, tocilizumab, directly into body cavities.
- RIOT 3: This program is in progress and is aiming to deliver an oncolytic viral agent, vvDD-hIL-2-RG-1, directly into tumors.
- RIOT 4: This program is still in development stages, but the goal is to deliver patient-derived immune cells (ACT/Adoptive Cell Therapy) into the pleural space (around the lungs).
- RIOT 5: Delivers patient-derived immune cells (ACT) into the peritoneal space (in the abdomen).
The overall RIOT program is complex and involved medical research that is being conducted by AHN to help our patients live fuller, healthier lives. A series of future studies — including RIOT6, RIOT7, and any future programs — will be developed based on the results of the earlier trials.
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Appointments
Regional Immuno-Oncology Trial Program(412) 578-HOPE
RIOT program team
The team, led by Dr. Patrick Wagner, offers patients access to innovative research and clinical trials focused on improving treatment outcomes for advanced abdominal cancers through immunotherapy and targeted drug delivery. Their work aims to provide new therapeutic and palliative (specialized care) options, ultimately improving the lives of patients with these challenging conditions.
Leadership
Principal investigator and primary contact
Principal investigator and system chair of AHN Cancer Institute
Co-investigators
Albert Donnenberg, PhD
AHNCI vice chair for translational research
Vera Donnenberg, PhD
Immunology faculty scientist
Neda Dadgar, PhD
Immunology faculty scientist
Casey Allen, MD
Surgical oncology
Alexander Shannon, MD
Surgical oncology
Kevin Xiao, PhD
Proteomics faculty scientist
Ali Zaidi, MD
Director of research, Esophageal and Lung Institute
Christopher Sherry, DO
Staff scientist
Hyun Park, MS
Staff scientist
Paige Mirsky, MS
Staff scientist
Shannon Altpeter, DMSc
Surgical oncology APP
Samantha Devine, MSPAS
Surgical oncology APP
Leslie Schlagel, MSPAS
Surgical oncology APP
Clinical trials and research
You participate in a clinical trial only if you volunteer to do so and meet criteria for inclusion in the study. You can stop participating in a trial at any time. If you want to be part of the RIOT trial, talk to your primary care doctor or oncologist. Most of these trials and check-ins occur at West Penn Hospital and Allegheny General Hospital (AGH).
RIOT 1
RIOT-1 (Regional Immuno-Oncology Trial-1) is a clinical study designed to assess the safety of injecting lipopolysaccharide (LPS) directly into abdominal tumors. LPS is a molecule from bacteria that can stimulate the immune system. The goal is to trigger the immune system to recognize and attack the tumor cells. LPS is injected directly into the tumors during a diagnostic laparoscopy (a minimally invasive surgical procedure). After the second surgery, the injected tumors are removed and analyzed to assess the immune response.
Participants are adults with peritoneal tumors that have spread from a primary gastrointestinal cancer and have at least two tumors suitable for injection. They must also be scheduled for a subsequent laparotomy (a more extensive surgery) where the injected tumors can be removed. The initial results from RIOT-1 showed no adverse events (complications) related to the LPS injection, indicating that this treatment is safe and well-tolerated. Learn more about RIOT 1.
RIOT 2
RIOT-2 (Regional Immuno-Oncology Trial-2) is a clinical study designed to assess the safety of administering an IL-6 blocker called tocilizumab directly into the pleural (chest) or peritoneal (abdominal) cavities in patients with malignant pleural effusions (MPE) or malignant ascites (MA). Tocilizumab is an IL-6 receptor antagonist, meaning it blocks the activity of the IL-6 protein. IL-6 signaling may play a role in the development of MPE and MA. Tocilizumab is delivered weekly via a catheter placed into the body cavity (pleural or peritoneal). The same catheter is used to drain excess fluid, helping to relieve symptoms. The study aims to assess the safety of the treatment and pave the way for future research into clinical applications of immunotherapy administered via this direct route. Learn more about RIOT 2.
RIOT 3
RIOT-3 is a Phase I dose-escalation trial testing the safety and feasibility of using an oncolytic vaccinia virus (vvDD-hIL-2-RG-1) delivered directly into tumors. This virus is engineered to express a membrane-bound form of IL-2, with the goal of stimulating an immune response specifically within the tumor microenvironment. The trial assesses the maximum tolerated dose (MTD) and/or maximum feasible dose (MFD) of the treatment. It also investigates the viral replication, pharmacokinetics, immune response, and potential anti-tumor effects in both injected and non-injected tumors. Learn more about RIOT 3.
RIOT 4 and RIOT 5
The RIOT4 clinical trial is a Phase 1 study designed to assess the safety and effectiveness of a novel Adoptive Cellular Therapeutic (ACT) immunotherapy in patients with cancer that has spread to the pleura or mesothelioma. This first-in-human trial involves creating an ACT product from the patient's own pleural infiltrating T-cells (PIT), which are isolated from pleural fluid, expanded in the lab, and enhanced with Interleukin-2 (IL-2) in the cell manufacturing facility at AHN West Penn. Prior to receiving the ACT product through a pleural catheter, participants undergo lymphodepleting chemotherapy. Following the infusion, IL-2 is administered via the catheter for two days to stimulate the enhanced PIT cells. The active treatment phase spans approximately three weeks, with follow-up visits scheduled over five years. Ancillary studies will be conducted to analyze pleural effusions and determine factors influencing the intervention's success or failure. RIOT5 is a parallel study for patients with abdominal metastatic cancers, in the peritoneal cavity. National clinical trial numbers are coming for RIOT 4 and RIOT 5.
Future trials
Future trials are ongoing to determine new approaches to treating abdominal and pleural tumors. The team is looking at including additional cytokine inhibitors, combination therapies, delivery devices, and biomarkers of efficacy that can aid in treatment. AHN researchers are examining immunological parameters and pharmacokinetic parameters as possible biomarkers of efficacy for immunotherapies.
Publications list
We have published multiple articles and presentations about this trial program. Our current publications list includes:
- Novel Approaches for Treating Advanced Abdominal Cancers [PDF]
- Intra-tumoral immunomodulatory therapy for advanced abdominal cancers using lipopolysaccharide: The Regional Immuno-Oncology Trial-1 (RIOT-1) protocol
- Intra-pleural and intra-peritoneal tocilizumab therapy for managing malignant pleural effusions and ascites: The Regional Immuno-Oncology Trial (RIOT)−2 study protocol
- Targeting interleukin-6 as a treatment approach for peritoneal carcinomatosis
- Characterizing the Immune Environment in Peritoneal Carcinomatosis: Insights for Novel Immunotherapy Strategies
Other active clinical trials
If you would like to participate in a clinical trial and help our innovative team discover groundbreaking cancer solutions, ask your doctor if you’re eligible to participate in one. Find currently active clinical trials that are open for participation.
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