Intratumoral vaccination protocol improved outcomes in mouse model of pancreatic cancer

Paul Basilio, MDLinx | March 22, 2017

Intratumoral vaccination in a mouse model of early stage resected pancreatic cancer induced an anti-tumor response that improved overall survival, according to investigators from the Rutgers Cancer Institute of New Jersey and the Rutgers Robert Wood Johnson Medical School.

Advertisement

Darren Carpizo, MD, PhD, surgical oncologist at Rutgers Cancer Institute, helped create the mouse model for the study.

Building on the past

The research group’s previous work focused on the investigational vaccine known as PANVAC, which contains gene additives that may stimulate a patient’s immune system to recognize and develop an immune response to the disease. In a phase I clinical trial, patients with pancreatic ductal adenocarcinoma were treated with PANVAC through direct tumor injection via endoscopic ultrasonography, which was followed with a PANVAC booster administered in the arm.

Results showed the median overall survival of the patients who received PANVAC was not significantly greater than that of patients with the same stage of disease treated with standard therapy.

Eight patients who did not have metastatic disease when they began the trial died following progression of the primary tumor in the pancreas. This result was unusual, according to the investigators.

As a result of that response, the researchers hypothesized that perhaps the vaccine could induce an immune response that protects against the development of metastatic disease, but it could not make an already formed tumor go away.

A new hope

After the initial research, the group aimed to further explore whether intratumoral vaccination would have a better chance at improving survival if it were administered to patients with early stage disease who could undergo removal of their pancreatic tumor following vaccination.

Before testing the theory in humans, the team first needed to see if the results could be identified in an animal model. No mouse models of early stage resectable pancreatic cancer were available, so they turned to Darren Carpizo, MD, PhD, surgical oncologist at Rutgers Cancer Institute. Dr. Carpizo’s laboratory then collaborated with the laboratory of Edmund C. Lattime, PhD, Rutgers Cancer Institute researcher and associate director for education and training, to conduct the vaccination experiments.

An antigen expressing vaccine was administered directly to the pancreas in mouse models, and a booster was given at regular intervals on days 4 and 18. This was followed by resection of the primary pancreatic tumor on day 28.

Investigators found that the tumors of the vaccine treated mice were smaller in size when compared with controls. Treated mice also displayed significant increases in immune populations that are associated with anti-tumor immunity.

In addition, the vaccinated group exhibited markedly prolonged survival vs controls, indicating that the vaccine allowed their immune system to protect them from acquiring metastatic disease and dying. 

“These findings will provide the necessary pre-clinical data to test a vaccine like PANVAC in humans with resectable pancreatic cancer,” said Dr. Carpizo. “Such a human trial has never been done before.”

The research was supported by a Rutgers Cancer Institute of New Jersey Gastrointestinal Oncology Pilot Grant to Drs. Carpizo and Lattime. Results were presented at the 70th Annual Society of Surgical Oncology Cancer Symposium in Seattle.

Advertisement