The parents of Amazon.com founder and CEO Jeff Bezos have pledged a $10 million donation to the Seattle-based Fred Hutchinson Cancer Research Center with an eye toward creating new therapies that trigger the immune system to seek out and kill cancer cells like a virus.
The offering from Jackie and Mike Bezos, one of the five largest gifts ever to the nonprofit research center, is being structured as a matching fund. The goal is to spark other private individuals to support the development of treatments that actively stimulate the immune system to fight cancer, known as immunotherapies. It’s the largest gift the Bezos family has made to support biomedical research.
“We’re very hopeful, yet mindful that undertakings of this nature are risky,” Jackie Bezos said in a statement. “There will, inevitably, be setbacks. This is why we are structuring the grant as a challenge, to help the Hutchinson Center secure, for the long term, a diverse group of supporters and to rally a community around science that has the potential to benefit us all.”
The idea of revving up the immune system to fight cancer has been around for almost a century, but even after three decades of intensified research, and more than $1 billion from biotech companies, there still isn’t an FDA- approved therapy that works this way. But Seattle-based Dendreon (NASDAQ: DNDN) reached a landmark earlier this year when it was the first to show, in a major clinical trial of 500 patients, that such an immune boosting-therapy could help prostate cancer patients live a median of four months longer than they otherwise would on a placebo, with minimal side effects. And at earlier stages of research, scientists at the National Cancer Institute, Johns Hopkins University, and the Hutch say they have made major strides in understanding how to provoke potent, long-lasting, and versatile immune responses that could change the fundamental reality of cancer treatment—which is still built on a bedrock of chemotherapy, radiation, and surgery.
The Hutch has a long history of expertise in immunology for cancer, dating back to E. Donnall Thomas’s pioneering work on bone marrow transplants as an effective way to treat leukemia and other blood malignancies. But it was research from the past couple of years, from the labs of four different Hutch scientists, that convinced the center that it was the right time to push forward with a more far-reaching immunotherapy research and development program now, says Fred Appelbaum, the senior vice president and director of the Hutch’s clinical research division.
Based on the recent progress, Hutch president Lee Hartwell and Appelbaum “became convinced that now is the time to press on the gas pedal,” Appelbaum says.
Before diving too deep into the science, I tried to gather some of the backstory. Appelbaum was pretty tight-lipped about the Bezos family other than to say, like most donors, they were introduced to the Hutch’s work by a “friend of the Center.” Like all private donations, it’s important because it will help the center recruit at least four new faculty, and will give them the leeway to test unproven ideas in the lab, and generate a little bit of data that’s needed in order to rake in bigger bucks from the biggest provider of funds for the center—the National Institutes of Health. It will also allow the center to advance further in clinical trials to gather more evidence on whether its treatments really work consistently or not.
So, what was it about the state of the art in the science that convinced the Bezos family to open up their checkbook? Appelbaum was a lot more talkative about this. He pointed to four important discoveries that have been made at the Hutch. (Warning: I’ve tried to distill this science into something reader-friendly for non-biologists, but it’s still technical.)
—Research by Cassian Yee that showed a long-term complete remission in a patient who got an immunotherapy after relapsing on prior treatment for melanoma that had spread through the body. Yee’s team drew some blood from the patient, and found a new way to grow up billions of additional “helper” T cells in the lab that were made to recognize a hallmark on cancer cells. The helpers are supposed to marshal growth factors to the so-called “killer” T cells that fight tumors. When the expanded number of “helper” T cells were re-infused into the patient, without any additional drugs, the tumors disappeared and the patient went into remission, according to this paper in the New England Journal of Medicine.
By provided added helper T cells, that enables the patient’s killer T cells to recognize a more diversified array of markers on cancer cells, Appelbaum says.
—Work by Stanley Riddell into how to make immunotherapies last longer. Scientists have long tried to separate out killer T cells of the immune system in the lab, grow them up in greater numbers, and re-infuse them, Appelbaum says. This can sometimes produce tumor shrinkage, but it usually doesn’t last very long, he says.
Riddell’s insight was to show how certain immune system cells have different kinds of “memory” to attack certain invaders. Most T cells “fight a battle that’s short-lived” against certain pathogens like flu, and then die off when the job is done. Yet some T cells, like those programmed by a measles vaccine, can remember the signature of that kind of invader and leap to the body’s defense for many years, Appelbaum says. Riddell’s work—which has been done in mice, not people—has shown that he can stimulate this longer-lasting immune memory against a cancer cell for a year, Appelbaum says.
—Philip Greenberg‘s lab has done experiments that take an up-close look at how T cells actually bind with the protein receptors on cancer cells, Appelbaum says. Usually these bonds are “loose,” or what scientists call low-affinity. By swapping out certain genes, Greenberg’s idea is to grow up T cells outside the body, and filter them so that patients get re-infused with the best type of cells that can form 100 to 1,000-fold tighter, stronger bonds to the receptor that scientists want to hit, Appelbaum says.
—Lastly, experiments by Thomas Spies have identified a molecule secreted by cancer cells that serves as a decoy, so that T cells get thrown off track before they can gang up on the tumors. The idea is to develop a targeted antibody that eliminates these decoys. That drug would be given before the patient has their revved-up T-cells re-infused, Appelbaum says.
Add it all together, and Appelbaum says this is why he wants to accelerate the research. “You can give people helper T cells to get a broader response, you can provide memory to make them last longer, and you can engineer them to have higher affinity for the target,” he says.
It’s too early to say there’s much in the way of medical proof that these ideas will work on a large scale, however. The Hutch may need help from biotech or pharmaceutical partners to commercialize the work. Immunotherapy has long been plagued by promising anecdotal responses that weren’t reproduced in the rigorous setting of randomized clinical trials. But Appelbaum insists that he’s optimistic about the chances of this new approach for melanoma, kidney cancer, breast cancer, sarcomas, gastrointestinal tumors, and other malignancies.
“It’s an educated bet,” he says. But, he added, he’d be “very disappointed” if it fails.
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