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breakthroughs from the lab

BRAIN CANCER VACCINE CAN EXTEND SURVIVAL RATE

Originally published Oct 2018

BY JULIA EVANGELOU STRAIT

Most people with glioblastoma, a form of brain cancer, die less than 18 months after diagnosis. But a multicenter clinical trial of a personalized vaccine that targets this aggressive cancer has indicated improved survival rates for these patients.

Dendritic_ cell
THE VACCINE IS MADE OF DENDRITIC, OR IMMUNE, CELLS THAT ARE EXPOSED TO A SMALL AMOUNT OF TUMOR TISSUE. NOW TRAINED TO SEEK AND DESTROY TUMORS CELLS, THEY ARE RETURNED TO THE PATIENT VIA INJECTION.
Image courtesy of the National Institutes of Health

The phase III clinical trial included 331 patients at over 80 sites in four countries, including the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. Participants in the trial were randomized to receive standard therapy plus the personalized vaccine, called DCVax-L, or standard therapy plus a placebo. Personalized vaccines are specifically tailored to individual patients.

The trial was designed to include twice the number of patients in the vaccine group as in the placebo group. And any patient in the trial was allowed to receive the vaccine if his or her cancer recurred or progressed after initial treatment. As such, almost 90 percent of all participants received the investigational vaccine.

Based on the analysis detailed in the study, all 331 patients in the trial (including those who did and did not receive the vaccine) had a median survival of just over 23 months. One-hundred patients had an average overall survival of 40.5 months — more than three years — and were designated as “extended survivors.” Investigators are particularly interested in the latter group’s response to the vaccine, though they don’t yet know whether everyone in this group received the vaccine since the trial is ongoing and remains blinded. The continued blinding means neither patients nor physicians know which patients are receiving the vaccine. But since the researchers reported that nearly 90 percent of all participants received the vaccine at some point, the chances that the extended survivors are getting the vaccine, rather than the placebo, are high.

“The overall patient population in the trial appears to live longer than we would typically see with current standard of care, and 30 percent of the patients have lived much longer than we would expect, given the typical course of this cancer,” says oncologist Jian Campian, MD, PhD, one of the study’s authors.

“In general, patients with this cancer live 15 to 17 months. The surprising part was that the 100 ‘extended survivors’ don’t appear to have the usual characteristics associated with a good prognosis. We are continuing to study these patients to understand why they have done so well.”

The personalized vaccine used was tailored to each patient. After surgery to remove as much of the tumor as possible, a small amount of tumor tissue was processed and then exposed to the same patient’s immune cells, called dendritic cells. Exposure to the tumor material essentially trains the dendritic cells to seek out and destroy tumor cells. These trained dendritic cells are returned to the patient as a vaccine injected in the arm. Relatively few vaccinations are needed: The first three are weeks apart; the next three are months apart; and then they continue with one vaccination every six months after the first year.

Campian says the vaccine had very few side effects, especially compared with standard treatment for this cancer, which includes surgery, radiation and chemotherapy. About 2 percent of participants (seven patients) experienced a serious adverse event — such as brain swelling or seizures — that may have been related to the vaccine, according to the researchers.

The trial, which was funded by the vaccine maker, Northwest Biotherapeutics Inc., is ongoing to allow for continued study of patients who are living beyond what is expected of those diagnosed with glioblastoma

90%

of all patients in the study received the investigational vaccine

331

patients, the total number in the study, had a median survival of 23 months

30%

of patients lived nearly two years longer than expected

Originally published by Washington University School of Medicine at medicine.wustl.edu/news


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