Vaccine exposes evasive colorectal cancer to an immune attack

Immunotherapy has taken hold as an effective treatment for a variety of advanced cancers, but so far, colorectal cancer has stubbornly resisted. 

However, research led by MD Anderson shows that resistance could be struck down. The recent international clinical trial helped expose a weak spot that leaves about 5% of colorectal tumors receptive to immune attack. (see the related story "5 years in, the Moon Shots Program is primed for continued progress" ) 

Now, a team in the Colorectal Cancer Moon Shot™ of MD Anderson’s Moon Shots Program™ is expanding on this discovery to benefit even more patients. 

Michael Overman, M.D., associate professor of Gastrointestinal Medical Oncology, led a Phase I clinical trial testing whether a special form of vaccination can recruit the immune response that’s missing in most patients. 

“Each patient is different, so we’re developing a personalized vaccine based on specific targets we identify on a patient’s tumor,” Overman says. “The initial question was ‘can we do this in a feasible amount of time for our patients?’ The pilot study showed we could.” 

Overman and colleagues are combining these tailored vaccines with an approved drug that protects and boosts immune response to see if the one-two punch can help more colorectal cancer patients. 

At first, analyzing a patient’s surgically removed tumor and developing a vaccine against 10 specific targets on the tumor took nine months, says Greg Lizée, Ph.D., associate professor of Melanoma Medical Oncology, whose research focuses on the immune system. Now the time from surgery to vaccine treatment is three months and falling. 

The trial opened in November 2016. By late summer, 17 patients with metastatic colon cancer had received customized vaccines. Several had their tumors shrink or remain stable temporarily, says Scott Kopetz, M.D., Ph.D., a professor of Gastrointestinal Medical Oncology and co-leader of the moon shot. 

In September, the team added to the vaccine regimen a drug called Keytruda that supports the immune system’s attack on tumors. 

How the vaccines work 

Some vaccines prevent cancer by destroying invading toxins or foreign substances that cause infection. For example, vaccines for the hepatitis B virus prevent liver cancer and vaccines for the human papillomavirus prevent cervical, anal and some throat cancers. 

Lizée and colleagues are developing a different type of vaccine called a therapeutic vaccine, which triggers an attack against established cancer. Earlier versions of such vaccines largely failed because they targeted single invading substances that were not mutated, so T cells that attack invaders often ignored them, he says. 

The team identifies “neoantigens” – targets that are unique to the tumor, using an exhaustive process made possible by recent technological advances. 

Ten such targets are found for each patient. A vaccine against all 10 neoantigens is developed and given on a set schedule during the clinical trial, along with Keytruda. 

Of the first 100 neoantigens identified for 10 patients, 98 were unique to the individual patients. 

Read how this unique treatment helped patient JT Burk get back to doing the things he loves in MD Anderson's Annual Report.