Will DNA Vaccine TetMYB Be a Game-Changer in Advanced Colorectal Cancer?

While immunotherapies have been mostly disappointing in the treatment of advanced colorectal cancer, Australian investigators think they may have a better shot at success with a new DNA-based vaccine treatment. They reported at Digestive Disease Week 2018 that clinical trials are now under way to investigate a new combination therapy that employs a novel DNA vaccine.

Lead researcher Robert Ramsay, PhD, BSc, who is group leader of the Gastrointestinal Cancer Center at Peter MacCallum Cancer Center, University of Melbourne, Australia, said cancer vaccines are getting closer to the clinic every day and are likely to provide a safer and more effective treatment for patients with colorectal cancer.

He said if the trial goes well, it could be “transformative” in terms of the standard of care for patients with advanced colorectal cancer. Ramsay said the pillars of treatment currently include surgery, chemotherapy, and radiotherapy. However, a DNA vaccine would add immunotherapy to the mix.

Gastrointestinal malignancy specialist Syed Kazmi, MD, who is an assistant professor of medicine at UT Southwestern Medical Center, Dallas, Texas, said this new stage of testing is promising because previous investigations with immunotherapies have not been very successful. “Gastrointestinal malignancies and colorectal cancers usually don’t respond with immunotherapy. In most cases, only about 5% respond,” Kazmi said in an interview with Cancer Network.

Ramsay and his colleagues tested their DNA vaccine TetMYB in combination with an anti-PD1 (programmed death 1) agent in mice that were induced to develop cancer. The murine tumors responded very well to the treatment, and the cancer was cured in approximately 50% of the animals. The mice were expected to live for only a couple of days or weeks, but about 50% survived up to 2 years. The vaccine also created an immune memory; when mice cured during the study were later re-challenged with the same tumor, it was immediately rejected.

Ramsay and his team are testing the new combination regimen in a phase I trial of 32 patients with advanced-stage colorectal cancer. Their study (ClinicalTrials.gov identifier: NCT03287427), called MYPHISMO, will investigate the effectiveness of TetMYB vaccine in combination with BGB-A317 (an experimental antibody) in patients with advanced or metastatic solid cancers, including colorectal or adenoid cystic cancer.

Medical oncologist Kian H. Lim, MD, PhD, who is with the Siteman Cancer Center and an assistant professor of medicine at Washington University School of Medicine in St. Louis, Missouri, said this approach is similar to several that have been tried in the past but failed to show significant benefits. “Although there is some novelty to this vaccine, the antigen, and fusion protein created, I would not call this approach transformative,” Lim told Cancer Network. “The data from the research paper were, in my critical opinion, not very impressive.”

He said the tumors continued to grow, albeit at a slower pace, in vaccinated mice in the preclinical trials. “So, it’s way too early to tell, and patients should not be given false hope. Having said this, I have to stress that novel treatment is needed in colon cancer. Clinical trials should continue to be opened, and are the only way to determine whether any novel strategy will work,” said Lim.