DNA-based vaccine for colorectal cancer to undergo first human trial
Researchers will test a two-pronged approach to treat advanced stage colorectal cancer (CRC) for the first time in humans.
Combining a DNA vaccine, which boosts the body’s immune response against tumors, with an antibody that blocks the body’s natural defense, may lead to the development of an effective treatment for late stage CRC.
This will be revolutionary for patients of late stage CRC where a cure is often not possible. Initial research leading up to this trial was presented at Digestive Disease Week® 2018.
Cancers arising from the large intestine are referred to as colorectal cancer (CRC). Colorectal cancer usually starts in the innermost layer (mucosa) and can grow through some or all of the tissue layers that make up the colon and rectum (submucosa, muscular and serosa ).
The extent to which cancer penetrates the various tissue layers including spread to other sites determines the stage of the disease.
“We are on the cusp of testing something that could be transformative for cancer treatment,” said Robert Ramsay, PhD, BSc, group leader of the Gastrointestinal Cancer Center at the Peter MacCallum Cancer Center at the University of Melbourne, Australia, and lead researcher of the study. “Cancer vaccines are getting closer to the clinic every day and are likely to provide a safer and more effective pillar of treatment for patients. Right now, the pillars of treatment include surgery, chemotherapy and radiotherapy, and vaccines would bring immunotherapy to the mix.”
The main reasons for failure of immunotherapies in past studies were due to the body’s natural cancer-fighting immune responses stimulated by vaccines to protect against a potentially uncontrollable immune response. The development of new antibodies to check this blockade is being used with the DNA vaccine in this study. This is expected to get past this obstacle by temporarily blocking the protective response.
In preliminary mouse studies, Ramsay and his colleagues tested the DNA vaccine TetMYB and anti-PD1 on mice that were induced to develop cancer cells. Tumors in the mice responded very well to the treatment, and the cancer was cured in about half of them. Mice were expected to live for only a couple of days or weeks, but about 50 percent of them survived up to two years.
All India data however shows it is the third most common cancer in women and the fourth most common in men.
The vaccine also created an “immune memory” in the animal studies. When mice cured during the study were later re-challenged with the same tumor, it was immediately rejected. “There is an immune memory for the vaccine,” Ramsay said.
In an article in the Indian Journal of Surgical Oncology in December 2017, researchers audited colorectal cancer cases in Tata Memorial Hospital Mumbai and found: “Eight hundred new patients with CRC were seen in the colorectal clinic in one year. The mean age was 47.2 years. Sixty-five percent were males.” All India data however shows it is the third most common cancer in women and the fourth most common in men.
Ramsay and his team are testing the regimen for the first time in humans in a phase 1 trial of 32 patients with advanced stage CRC. The study is designed to test safety and, if safety is shown, to allow all patients in the trial to receive the full treatment.
Researchers hope immunotherapy will prevent against hyperactive immune response.
