Vaccine Spurs Immune Response to Fight Aggressive Cancers in Mice

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In a step toward personalized vaccines against cancer, scientists report they have developed an immune-system therapy that knocks out several types of aggressive tumors in mice.

German researchers said the findings, reported April 22 in the journal Nature, could lead to a “blueprint” for developing tailored vaccines for a range of cancers. Such vaccines would be designed for individual patients, based on the specific genetic mutations in their tumors.

The goal would be to enlist the immune system to attack the cancer — somewhat like the way standard vaccines get the immune system to prevent infections such as measles and chickenpox.

Researchers have long been testing therapeutic vaccines to treat certain cancers, but it hasn’t been an easy road.

“For decades, we’ve had cancer vaccines that fail to work, and we haven’t really understood why,” said Dr. Lynn Schuchter, a medical oncologist at the University of Pennsylvania and chair of the cancer research committee for the American Society of Clinical Oncology.

But recent advances in understanding and harnessing the immune system’s power could be changing that, according to Schuchter, who was not involved in the new study.

“These are pretty dramatic results in the mouse model [of human cancers],” she said. “Studies like this are paving the way for effective vaccine approaches.”

However, animal research does not always pan out in human trials.

The researchers, led by Dr. Ugur Sahin, of Johannes Gutenberg University in Mainz, Germany, used an approach that targets specific mutations in a given tumor.

The mutations unique to cancer cells are an “ideal” target for vaccines, according to Sahin’s team. That’s because the mutations are absent in healthy cells, and could stimulate the immune system to recognize tumors as foreign invaders and attack them.

However, since each person’s cancer has a unique set of mutations, scientists are working toward customized vaccines — tailored to target an individual patient’s tumor.

Earlier this month, researchers reported initial results on just such a therapy. They developed personalized vaccines for three people with advanced melanoma, the deadliest form of skin cancer.

In each case, the vaccine triggered an increase in T-cells that could recognize the patient’s cancer cells — though the researchers stressed it’s not yet clear whether the approach can actually beat back melanoma and extend people’s lives.

The vaccines used in the current study are molecularly different from those in the melanoma trial, explained Dr. Alexandra Snyder Charen, an oncologist and immunotherapy researcher at Memorial Sloan Kettering Cancer Center, in New York City.

The latest approach could potentially “stimulate the whole immune system, rather than just killer T-cells,” said Charen, who was not involved in the study.

Sahin’s team started by identifying specific mutations in mouse tumors that were capable of spurring a response in T “helper” cells — key immune system sentries that activate other parts of the immune system. From there, the researchers created customized vaccines containing synthetic genetic sequences. In the end, mice that were vaccinated showed a strong immune response and survived longer than untreated mice did.

What’s more, the customized vaccines worked in mouse models of not only skin cancer, but also colon and lung tumors.

“That suggests the approach could be broadly applicable” to different cancer types, Charen said.

But she also urged caution. The findings are based on mice — and a small number of mice at that, Charen pointed out.

“There is cause for optimism and excitement,” she said. “But this needs to be validated in further research.”

An initial human trial involving melanoma patients has already begun, Sahin’s team said.

If custom vaccines do prove effective against various cancers, there will be “technical hurdles” to creating and using them in the real world, according to Schuchter. But she also said those issues are surmountable.

Vaccines are not the only form of cancer immunotherapy — a general term for treatments that help the immune system find and destroy tumors. Some, such as drugs known as checkpoint inhibitors, are already used for some cancers.

It was traditionally thought that many cancers, such as colon and lung, were not “immunogenic” — or capable of being “seen” by the immune system, Charen explained.

But research has changed that thinking, and the goal now, she said, is to make immunotherapy work against all cancers.

More information

The American Cancer Society has more on cancer vaccines.

Source: HealthDay

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