Novel vaccine for colorectal cancer shows positive phase I results

April 25, 2019

PHILADELPHIA -- A new colorectal cancer vaccine showed positive results in the phase 1 clinical trial to demonstrate that the approach is safe. The patients treated had no signs of serious adverse events and samples of their blood contained markers of immune activation -- an early indication that the vaccine could activate immune cells to fight colorectal tumors and metastases. Further tests to determine if the vaccine is effective at slowing tumor growth are forthcoming.

The results were published in the Journal for ImmunoTherapy of Cancer.

Colon cancer, especially in younger people, is on the rise and is currently the second highest cause of cancer deaths in the US and worldwide. Surgery can cure the disease in many patients, but prognosis is poor for those with recurrence of their disease. If it proves effective in larger-scale trials the vaccine, developed by researchers at Jefferson (Philadelphia University + Thomas Jefferson University), could train the patient's immune system to attack the colon cancer that had already spread before the surgery.

"There is an urgent need to understand what fuels colorectal cancer growth, and to harness that knowledge for developing novel therapies. 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. This is a true milestone-- made possible through the scientists and clinicians in our colorectal cancer team working in synchrony", said Karen E. Knudsen, PhD, EVP of Oncology Services and Director of the Sidney Kimmel Cancer Center -- Jefferson Health.

In earlier preclinical work in mice, Jefferson researchers demonstrated how the design of their vaccine worked. 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, PhD, 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 first author, Adam Snook, PhD, 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.

The current clinical trial enrolled 10 patients with stage I or II colon cancer. Patients were given one dose and came back for blood draws 30, 90, 180 days after immunization. Patients experienced some discomfort at the injection site, but reported no serious side effects of the vaccine. 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 the cancer to come back.

"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 four 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.
-end-
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. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30 CA056036.

Article reference: Adam E. Snook, Trevor R. Baybutt, Bo Xiang, Tara S. Abraham, John C. Flickinger Jr, Terry Hyslop, Tingting Zhan, Walter K. Kraft, Takami Sato and Scott A. Waldman, "Split tolerance permits safe Ad5-GUCY2C-PADRE vaccine-induced T-cell responses in colon cancer patients," Journal for ImmunoTherapy of Cancer, DOI: 10.1186/s40425-019-0576-2, 2019.

Media contact: Edyta Zielinska, 215-955-7359, edyta.zielinska@jefferson.edu.

Thomas Jefferson University

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.