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
By Peter Fong
Associate Director of Oncology Business Development
Great science has always been at the core of Genentech, just as it is at any cutting-edge biotech company or top academic lab. And because collaboration is often crucial to great science, partnering is a key aspect of our culture. Turning groundbreaking inventions into transformational medicines takes the collective effort of many people working together to ensure that the technology receives all the resources and wide-ranging expertise needed to navigate the complexities of drug development.
BioNTech brings to this partnership a potentially first-in-class personalized cancer vaccine (PCV) with an existing end-to-end process from tumor sequencing to mRNA manufacturing and drug delivery formulation.* In addition, its scientists have demonstrated that their vaccine can generate a tumor-specific immune response. They have thought through the immunological intricacies of their system just as we would have if faced with the same challenges.
Genentech brings a robust and wide-ranging pipeline in which to integrate BioNTech’s PCV, and the manufacturing and regulatory expertise needed to realize such a novel approach. We also bring industry-leading experience in taking cancer treatments from the lab to the clinic and a global oncology commercial organization to market the vaccine once it’s ready.
Our partners appreciate that we’ll put all of our might behind the most novel, high-quality science. Therapeutic novelty doesn’t intimidate us; it drives us. In working with BioNTech, our shared goal is to create a streamlined process in which each personalized cancer vaccine can be built within just weeks of receiving a person’s tumor sample. We hope to make PCVs a clinical reality, and to push forward our decades-long commitment to transforming cancer treatment.
*The completion of this agreement is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act, and is expected to occur in the fourth quarter of 2016.
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.
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.”