Colon Cancer Vaccine Candidate Produced Antibody Responses in 10% of Patients

A new colorectal cancer vaccine candidate Ad5-GUCY2C-PADRE showed positive results in a small phase 1 clinical trial in humans. 

These 10 patients with stage I or II colon cancer displayed no signs of serious adverse events from the Ad5-GUCY2C-PADRE vaccine and samples of their blood contained markers of immune activation. 

This means the vaccine candidate could activate immune cells to fight colorectal tumors and metastases. 

Specifically, antibody responses to GUCY2C were detected in 10 percent of patients, while 40 percent exhibited GUCY2C-specific T-cell responses. 

Patients were given 1 dose of the Ad5-GUCY2C-PADRE vaccine and came back for blood draws 30, 90, 180 days after immunization. The blood samples showed activation of "killer T cells," the immune cell type the researchers had expected. 

These killer T cells are responsible for finding and killing colon cancer cells that are responsible for causing cancer to come back. 

If it proves effective in larger-scale trials the vaccine, developed by researchers at Jefferson, could train the patient's immune system to attack the colon cancer that had already spread before the surgery. 

This research is important since colon cancer in younger people is increasing and is currently the 2nd highest cause of cancer deaths in the US and worldwide. 

"This pivotal study provides some of the first evidence that it may be possible to safely direct a patient's own immune system to seek and destroy this cancer type", said Karen E. Knudsen, Ph.D., EVP of Oncology Services and Director of the Sidney Kimmel Cancer Center -- Jefferson Health, in a press release. 

Tumor vaccines have historically been developed against a sort of molecular sign-post for cancer. Because they come from normal cells, cancer cells share nearly all of the same molecules, making it difficult for the immune system to differentiate normal from cancerous. 

Tumor antigens are molecules that the immune system can recognize as different from normal. 

In colorectal cancer, one such molecule called GUCY2C was identified by Scott Waldman, MD, Ph.D., the Samuel M.V. Hamilton Professor and Director of the Gastrointestinal Cancer Program of the Sidney Kimmel Cancer Center -- Jefferson Health. 

The vaccine developed by the first author, Adam Snook, Ph.D., Assistant Professor in the Department of Pharmacology and Experimental Therapeutics, Dr. Waldman and others, works by activating the immune system against the GUCY2C molecule. 

By joining the GUCY2C molecule with a molecule that boosts the immune reaction called PADRE, and loading it into an adenovirus vector, the researchers engineered a vaccine that could specifically target the colon cancer. 

"We are preparing for a phase II study that will begin recruiting patients this fall," says Dr. Snook. "We used lessons learned in the first study to modify the vaccine to hopefully make it even more effective." 

Since starting the trial, the researchers found that cancers other than colorectal cancer also express GUCY2C, including gastric, esophageal and pancreatic cancer. 

These are actually among the deadliest cancers. In fact, together with colorectal cancer, these 4 cancer types account for 20 percent of all cancer-related deaths. 

"The goal of the study to begin this fall is to show that version 2.0 of the vaccine is even better and that it may benefit a much bigger group of the overall cancer patient population," says Dr. Snook.

This work was supported by the National Institutes of Health R01 CA170533 and Targeted Diagnostic and Therapeutics Inc. A Research Starter Grant in Translational Medicine and Therapeutics from the PhRMA Foundation and the Margaret Q. Landenberger Research Foundation. The Alfred W. and Mignon Dubbs Fellowship Fund and a PhRMA Foundation Pre-Doctoral Fellowship InPharmacology/Toxicology. This work was supported, in part, by a grant from the Pennsylvania Department of Health (SAP #4100051723). The Department specifically disclaims responsibility for any analyses, interpretations or conclusions. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30 CA056036.

No conflicts of interest were disclosed.

Media contact: Edyta Zielinska, 215-955-7359, [email protected].