Positive phase I results for colorectal cancer vaccine

Friday, 03 May, 2019

Positive phase I results for colorectal cancer vaccine

A new colorectal cancer vaccine, developed by US researchers, has shown positive results in a phase I clinical trial to demonstrate that the approach is safe. The trial was described 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. The new vaccine, developed by researchers at Jefferson (Philadelphia University + Thomas Jefferson University), aims to train the patient’s immune system to attack colon cancer that has already spread before surgery.

“There is an urgent need to understand what fuels colorectal cancer growth, and to harness that knowledge for developing novel therapies,” said Karen E Knudsen, PhD, EVP of Oncology Services and Director of the Sidney Kimmel Cancer Center – Jefferson Health. “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.”

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. Tumour antigens are molecules that the immune system can recognise as different from normal. In colorectal cancer, one such molecule — known as GUCY2C — was identified by Scott Waldman, MD, PhD, Director of the Gastrointestinal Cancer Program of the Sidney Kimmel Cancer Center.

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

Meanwhile, 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.

Further tests to determine if the vaccine is effective at slowing tumour growth are forthcoming, with first author Adam Snook, PhD, saying a phase II study will begin recruiting patients in the American autumn.

“We used lessons learned in the first study to modify the vaccine to hopefully make it even more effective,” Dr Snook said.

Since starting the trial, the researchers have found that cancers other than colorectal cancer also express GUCY2C, including gastric, oesophageal and pancreatic cancer. Together with colorectal cancer, these four cancer types account for 20% 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,” Dr Snook said.

Image credit: ©stock.adobe.com/au/Csák István

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