By Jayson De Leon
WASHINGTON — In an apparent reversal, the federal government said last week that patients with a genetic vulnerability to cancer could be immunized with a fourth shot of a vaccine that, if successful, might prevent cancer.
The move comes as a data analysis on the fourth shot suggests it might be more effective at blocking a common type of immune system failure, according to a report released by the U.S. Food and Drug Administration.
The new vaccine, CTLA-4, was approved last year by the agency for leukemia and other cancers, along with some other diseases. Other types of cancer are being studied for the first time, including lymphoma and other gastrointestinal cancers.
Still, the FDA said that the latest findings should not be viewed as a final approval for the vaccine. To qualify for a fourth shot, patients would have to have received two prior shots of the vaccine before the most recent one. It has not yet been approved for use in any group outside of people with a genetic vulnerability to cancer.
That genetic vulnerability – called antigenic enrichment, or EV1 – depends on the presence of one of the disease-promoting proteins known as antigens in the person’s tumor. In the current vaccine, the immune system is able to fight off cancer by rejecting the antigens. As a result, cancers that are resistant to that ability can stay alive.
The four-shot regimen alters the vaccine so that it protects against the presence of antigens by blocking and suppressing pathways that activate the immune system’s T cells, which represent a powerful weapon against cancer.
In the latest study, researchers evaluated the performance of CTLA-4 in 50 patients with solid tumor cancers. Foureen of those patients had the genetic vulnerability to EV1. The patients were all enrolled in the Phase III CTLA-4 Clinical Trial for Patients with Known or Undiagnosed Autoimmune Celiac Disease and/or Nephrotic Syndrome.
Two-thirds of the patients experienced tumor shrinkage, while others experienced improvements in the severity of their disease. Overall, 8 percent experienced a complete response in which their tumor disappeared completely.
“These results are promising as we saw a number of tumor reduction and stabilization in patients with previously diagnosed EV1,” said Dr. Victor Moreno, director of the John C. Danforth Cancer Center at the University of Missouri. “Clearly, this vaccine is well-tolerated and appears to be effective in melanoma, although we need additional data.”
According to the report, those results are not consistent. Some patients were eligible for the fourth shot of the vaccine but were not offered it.
Investigators said the findings, which have not yet been published in a peer-reviewed medical journal, suggest that people with a genetic vulnerability to cancer “may benefit more from the immunotherapy” than had been expected, given that they had already been vaccinated twice.
The FDA said Monday that it “is working to allow physicians and patients to access and use this novel vaccine vaccine in children who have been previously vaccinated for auto-immune diseases with good tolerability.”
In addition, FDA Commissioner Dr. Scott Gottlieb, in a Sept. 11 blog post, wrote that if the four-shot regimen is safe and effective in children, it would change the use of the vaccine.
“With the exception of some autoimmune diseases, the body responds well to immunotherapy,” Gottlieb wrote. “What this means is that most cancers can be treated with immunotherapy. But not all, and right now that’s the case.”
According to the FDA, most cancers that can be treated with immunotherapy have one or more of the three biological markers known as CD8+ T cells.
Moreno said he expected that immunotherapy to be increasingly used in adults with cancers that are resistant to the vaccine.
“With the exception of perhaps a few cases, such as prostate cancer, virtually every cell cancer will respond with T cells” to immunotherapy, he said.
The immune response to the vaccine, he added, “has been promising, and we can only hope that it will continue to improve.”