Decoding Cancer

Personalized medicine has revolutionized what it means to hear, “You have cancer.” The first step after diagnosis is often to analyze the tumor for genetic mutations that can help identify the most effective targeted treatments. People who find a match can sometimes live free of cancer for many years.

But many people still don’t find a match, and even the most targeted therapies work differently across groups of people with similar genetic mutations. So after producing some encouraging pre-clinical results, Genentech has entered into an agreement with BioNTech, an expert in next-generation immunotherapies, to develop a cancer vaccine that would be truly personalized.

Unlike a traditional vaccine, this would not be preventive — a person would receive the vaccine as treatment after diagnosis. But just like a shot for measles or chicken pox, a cancer vaccine would prime the immune system to home in on specific molecular targets. Vaccines changed the course of human history by sharply reducing the ravages of polio, diphtheria, smallpox and other infectious diseases — why not try them against cancer?

Partners for a New Path

Partners for a New Path

By Peter Fong, Associate Director of Oncology Business Development

A Hidden Fingerprint

Here’s how receiving a personalized cancer vaccine would work: First, a doctor would submit a person’s tumor sample for genetic sequencing. Sophisticated algorithms capable of analyzing large amounts of genetic data would decode that information, and reveal the unique targets with the most potential to train the immune system to attack that person’s cancer. A vaccine would then be custom-built and sent back to the doctor for administration, potentially alongside other medicines. All of this would occur in a matter of weeks – crucial efficiency since cancer treatment is a race against time.

“What’s truly revolutionary about this approach is that each vaccine uses a common molecular backbone – mRNA – that is uniquely tailored to an individual patient,” says Todd Renshaw, Global Head of Clinical Contract Manufacturing. “It’s the next step in personalized medicine.”

It’s also incredibly difficult to engineer, says Lélia Delamarre, Scientist in Cancer Immunology. Unlike infectious diseases, cancer doesn’t infiltrate the body from outside; tumors arise from the body’s own tissues, making it harder for the immune system to detect them.

“Vaccines work by exposing the immune system to ‘non-self’ proteins known as antigens, priming it to recognize and eliminate the invaders. But in the case of cancer cells, most proteins are the same as those on healthy cells. This makes it hard to identify which antigen to use in a vaccine,” Delamarre says.

There are, however, alterations to some proteins that set cancer apart. These “neoantigens” are the result of random genetic mutations that occur as a tumor grows. Together, the collection of neoantigens on the cell surface is unique to each person’s cancer – like the bumps and grooves of a fingerprint. In 2014, Delamarre’s lab published a Nature paper showing that it’s possible to read those molecular fingerprints by analyzing a tumor’s genome.

Better Together

Activating the immune system based on a tumor’s molecular fingerprint would be a great achievement. But the interplay between the immune system and tumor cells is a complex process (see The Cancer Immunity Cycle), and vaccines only affect part of it. Other immunotherapies target complementary steps in the process – for example, checkpoint inhibitors disable cancer cells’ ability to protect themselves from an immune system attack. By combining a personalized cancer vaccine with this type of medicine, we may create a regimen that’s even more effective at eliminating the disease.

“We are truly advancing the cutting edge of cancer treatment,” says Scott Holden, Senior Group Medical Director. “Together with BioNTech, our goal is to help realize the boundless potential for personalized cancer vaccines and deliver the potential of immunotherapy to as many people as possible.”