Cancer vaccine along with immunotherapy shrinks liver tumors

Liver cancer is the sixth most common cancer in the world. Researchers estimate that 905,700 people will be diagnosed with liver cancer in 2020, and that number is expected to reach 1.4 million by 2040.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for more than 80% of all cases.

One of the newest treatment options for HCC is immunotherapy, a treatment that uses a person's own immune system to fight cancer. However, past studies show that only 15-20% of HCC diagnoses respond to immunotherapy and about 30% may be resistant.

Now, results from a preliminary clinical trial show that people with HCC who received immunotherapy and a personalized tumor vaccine were twice as likely to have their tumors shrink than those who received immunotherapy alone.

How does a personalized cancer vaccine work?

This preliminary clinical trial was conducted for GNOS-PV02, a personalized DNA vaccine created by Geneos Therapeutics.

"Essentially, GNOS-PV02 aims to (train) the immune system to recognize the antigens present in cancer so that the immune system can better recognize and attack cancer cells," explained lead study author Mark Yarchoan, M.D., Ph.D., assistant professor of medicine in the Department of Oncology at the Johns Hopkins Kimmel Cancer Center.

"The vaccine is personalized for each individual cancer patient. Just as each person has a unique fingerprint, each cancer has its own set of unique antigens that result from unique DNA mutations within the cancer," Yarchoan said.

"To create a personalized vaccine, first a cancer biopsy is taken and the cancer DNA is sequenced to identify potential unique antigens within the cancer. A personalized vaccine is then manufactured that encodes the unique antigens identified in the analysis of the tumor biopsy." - Mark Yarchoan, M.D., lead author of the study

Liver cancer vaccine in combination with immunotherapy

GNOS-PV02 was used in combination with the immunotherapy drug pembrolizumab, known by the brand name Keytruda.

The Food and Drug Administration (FDA) granted Reliable Source approval to pembrolizumab for the treatment of HCC in November 2018.

"Despite recent advances in the treatment of HCC, only a small proportion of patients respond to current systemic treatments, and the prognosis for patients with advanced disease is worse than for most other tumor types," Yarchoan said.

Yarchoan noted that until recently, most cancer vaccines have not been used in clinics, and cited a number of potential reasons why.

"One reason is that previous cancer vaccines typically targeted antigens that were not sufficiently cancer-specific," he said. "Most cancer antigens are unique to a particular type of cancer, and the technology to personalize cancer vaccines has only recently become possible."

"But another reason cancer vaccines have generally not been successful in the clinic is that they have been used in late-stage cancers without any other immunotherapy," Yarchoan continued.

"We have learned that vaccines can deplete immune cells before they can destroy cancer cells. For this reason, modern cancer vaccines are often combined with other immune-activating therapies such as pembrolizumab. This prevents the vaccine-induced T-cell depletion," he explained.

Liver cancer vaccine shrinks the tumor

Researchers recruited 36 participants for this clinical trial. All participants received a combination of the GNOS-PV02 vaccine and pembrolizumab.

At the end of the study, the researchers found that nearly one-third of the participants had tumor shrinkage, about twice as many as people seen in studies of HCC immunotherapy alone.

In addition, about 8% of the study participants had no evidence of tumor after taking the combination treatment.

"The response rate in this study is quite high, and I think it's unlikely that pembrolizumab alone did that - it supports the idea that the vaccine contributed to the observed efficacy," Yarchoan said.

"I think it's also notable that the response rate was higher than pembrolizumab alone, without a significant increase in toxicity."

"I think the results are very encouraging, but larger randomized studies are needed to confirm the efficacy of personalized cancer vaccines and to determine the optimal treatment sequence for their use. Geneos Therapeutics is planning larger clinical trials, and I am hopeful that such studies will confirm that this vaccine is an active agent." - Mark Yarchoan, M.D., lead author of the study

Are personalized vaccines the future of cancer treatment?

After studying the results of this study, Anton Bilchik, M.D., M.P.H., an oncologic surgeon and chief medical officer and director of the gastrointestinal and hepatobiliary program at St. John's Cancer Institute at Providence in Santa Monica, California, said he was "absolutely astounded" by the results of this study. Results of this early vaccine trial. Results of this early vaccine trial.

"HCC is one of the most common cancers in the world, and it tends to be very resistant to treatment," Bilchik explained. "Immunotherapy has recently been introduced as a possible treatment option for patients with advanced HCC, but response rates to immunotherapy have not been high."

"The goal of this study is to take a patient's own tumor and create a personalized vaccine that doubles the response of the immunotherapy currently used to treat HCC," he continued. "Not only are the results striking, but these are patients in whom first-line treatment has failed and who are not amenable to resection or transplantation."

"(This is) very encouraging news," commented Martin Gutierrez, M.D., M.P.H., director of the phase I study at the John Thurer Cancer Center at Hackensack University Medical Center in New Jersey. "(The next step of the study should be) a larger phase II study of first-line therapy."

When asked if we will see more personalized cancer vaccines in the future, Bilchik said absolutely.

"This is the future. And what makes this approach unique is that they're not only using the patient's own biopsy tumor cells to identify these mutations, but they're taking it a step further by using these computational algorithms to predict which genes might be recognized by the patient's own immune system. So this is moving into the realm of really advanced technology and then eventually to artificial intelligence." - Anton Bilchik, MD, PhD, Surgeon General

The study was published in the journal Nature MedicineTrusted Source.