Personalized vaccine helps patients fight against ovarian cancer FDA launches investigation into unauthorized herpes vaccine

In early research that extends the possibilities of immunotherapy to a killer feared by women, a personalized vaccine helped patients with ovarian cancer mount a stronger defense against their tumors and substantially improved their survival rate.

The vaccine was tested in a preliminary clinical trial and used along with standard chemotherapy and an immuneboosting agent.

The experimental therapy, described this week in the journal Science Translational Medicine, weaves together a number of approaches that are collectively driving innovations in cancer treatment.

Because the treatment uses the patient’s immune cells as a sort of T-cell training force, it is an immunotherapy. Because it uses the distinctive proteins on a patient’s own tumor as homing beacons, it is a targeted therapy. And because a patient’s own cells are harvested and returned to her, it is personalized therapy.

Rather than round up a patient’s T cells and re-engineer them in a lab to find cancer (the service provided by the new leukemia immunotherapy drug Kymriah), this treatment harvests a class of immune “helpers” called dendritic cells. Using ground-up cells from a patient’s tumor, researchers trained the dendritic cells to recognize and attack that specific malignancy. When these fortified cells were reintroduced into the patient, they passed on their training to the immune system’s army of killer T cells and sent them into battle.

Among 10 women with advanced ovarian cancer who got injections of the personalized vaccine once every three weeks — along with the medications cyclophosphamide and bevacizumab (marketed as Avastin) — eight showed a strong immune response and were still alive after two years.

In a comparison group of 56 patients that got standard chemotherapy alone, only half were still alive at the two-year mark.

Among a second cohort of 10 patients who got bevacizumab and dendritic cell vaccine alone (but no cyclophosphamide), only 30 percent survived to the two-year mark.

The study’s primary aim was to test the safety of the vaccine in combination with the other drugs.

Among these study subjects, as well as in subsequent cohorts of research subjects, the vaccine has been “so safe it’s unbelievable,” said study leader Dr. Janos L. Tanyi, a gy- necologist at the University of Pennsylvania. At worst, subjects have reported brief bouts of tiredness or flu-like symptoms, he said.

The same approach may also prove helpful in combating solid tumors in different organs, Tanyi said.

If ever there were a cancer ripe for a more effective new treatment, it’s ovarian cancer. As the fifth-leading cause of cancer death in the United States — and the most deadly of gynecological cancers — it claimed the lives of more than 14,000 American women in 2014, according to the Centers for Disease Control and Prevention.

Because there is no effective screening mechanism for ovarian cancer, it’s often not detected until it has reached an advanced stage. For 85 percent of women in whom it is diagnosed, a combination of surgery and chemotherapy does not succeed in driving the malignancy into remission, and it recurs.

A personalized ovarian cancer vaccine is likely years away from widespread use in patients. Scientists will likely have to find a way to make larger supplies of vaccine with a limited supply of tumor cells, Tanyi said. Meanwhile, researchers are already finding new ways to enhance the vaccine’s effectiveness, he added.

As in other immunotherapy trials, Tanyi has found that some patients were able to halt their cancer’s progression with continued booster shots of vaccine. For some women, the vaccine appears to have driven the cancer into remission entirely.

The Food and Drug Administration has launched a criminal investigation into research by a Southern Illinois University professor who injected people with his unauthorized herpes vaccine, Kaiser Health News has learned.

SIU professor William Halford, who died in June, injected participants with his experimental herpes vaccine in St. Kitts and Nevis in 2016 and in Illinois hotel rooms in 2013 without safety oversight that is routinely performed by the FDA or an institutional review board.

According to four people with knowledge about the inquiry, the FDA’s Office of Criminal Investigations is looking into whether anyone from SIU or Halford’s former company, Rational Vaccines, violated FDA regulations by helping Halford conduct unauthorized research. The probe is also looking at anyone else outside the company or university who might have been complicit, according to the sources who asked not to be identified because of the sensitivity of the matter.

The FDA rarely prosecutes research violations, usually choosing to administratively sanction or ban researchers or companies from future clinical trials, legal experts said. Even so, the agency is empowered to pursue as a crime the unauthorized development of vaccines and drugs — and sometimes goes after such cases to send a message.

In this case, human-subject violations would be deemed especially serious given Halford was not a medical doctor and had injected people with his experimental vaccine without any routine oversight, experts said.

“Since the research appears to be an effort to totally evade FDA oversight and is egregious, it makes sense the FDA would investigate it as a criminal matter,” said Patricia Zettler, a former FDA lawyer who was told of the criminal investigation by KHN. “There is a deterrent effect for others who might consider this a very brazen way to get out of human subject and FDA requirements.”

The FDA declined to comment. Rational Vaccines did not respond to requests for comment. An SIU spokeswoman said, without elaboration, “The government is investigating and we are cooperating.”

Any resulting criminal prosecution from the investigation could have political ramifications.

Rational Vaccines was cofounded with Hollywood filmmaker Agustin Fernandez III and the company received millions of dollars in private investment from investors after the Caribbean trial, including from billionaire Peter Thiel.

Thiel, who for months has refused to respond to questions from KHN, contributed to President Donald Trump’s campaign and is a high-profile critic of the FDA. Thiel is part of a larger libertarian movement to roll back FDA regulations to speed up medical innovation.