News Article | April 13, 2016
Sean Parker is deathly allergic to peanuts. If he accidentally eats a rogue nut and doesn't receive an epinephrine injection, he will stop breathing. Parker's struggle with life-threatening allergies hasn't stopped him from achieving fortune (as the first investor in Facebook), fame (Justin Timberlake played him as a charismatic hustler in the film The Social Network), and a track record for changing entire industries (remember Napster?). It did, however, inspire him to spend countless hours in an Internet rabbit hole researching the mysteries of the human immune response. "I'm totally fascinated by the immune system," he told me by phone this week, while trying to escape the New York rain. "Like my interest in other scientific fields, I took a deeper dive and got more and more invested." In December 2014, he got his feet wet by making a $24 million donation to the Stanford University School of Medicine, which is earmarked for allergy research. Today, he is announcing the $250 million-funded Parker Institute, a research effort to develop targeted therapies to treat cancer, which is noteworthy in its ability to evade the immune system. That's the single largest financial contribution to the field of immunotherapy ever. It's also Parker's most ambitious effort in biotech. To discover breakthrough therapies, Parker has personally helped recruit a brain trust of more than 40 laboratories and 300 researchers from the top cancer centers, including MD Anderson, Memorial Sloan Kettering, Penn Medicine, Stanford, and the University of California, San Francisco (UCSF). Strategic advisers include Jeff Huber, a longtime Googler who is now working to develop a blood test for cancer detection, and executives from a variety of pharma companies including Amgen and Merck. Dr. Jeff Bluestone, a well-known researcher and a former provost at UCSF, is leading the initiative as its chief executive offer. "I've been following the explosion of cancer immunotherapies in the past five years," Bluestone says. "I met Sean a few times, and he asked if I'd join." Parker seems confident he can create momentum outside the ivory towers of medical research, even though $250 million is a drop in the bucket compared to the costs of drug development, which is typically in the billions. The Parker Institute is hoping that its partners, the pharmaceutical companies, will fund the early clinical trials and shoulder the costs of bringing a new therapy to market. "From my perspective as an entrepreneur, I know we can see results faster," he says. He's identified two major flaws with research today: The lack of collaboration between researchers, and the frequent intellectual property disputes over new technologies. As a condition of partnering with the Parker Institute, researchers are expected to work with each other instead of pursuing personal glory. They must also agree to license any new technology they develop through the institute. After watching scientists behind one of most important biotech breakthroughs in recent history, a gene-editing technology known as CRISPR, get embroiled in a messy legal battle over patents, Parker is desperate to avoid a scenario in which technologies sit on the shelf for decades while researchers duke it out in court. "I joke around that if you were to roll back the clock and design an industry or field that would produce a breakthrough technology for treating patients and curing disease, this is the last structure you would come up with," Parker adds. In 2011, Parker's good friend, the legendary film producer Laura Ziskin, passed away from breast cancer. The two had frequently discussed the potential of immunotherapy, which was also a subject close to Ziskin's heart. After she died, Parker set about quietly deploying capital into immunotherapy. "I set up a dream team in the scientific establishment, which hadn't embraced the idea yet," he says. But the field quickly entered into a kind of renaissance. Today, immunotherapy is central to the Obama Administration's "moonshot" to cure cancer. Vice President Joe Biden recently predicted that immunotherapy will progress cancer research more in the next 10 years than it has in the past 50. Broadly speaking, cancer immunotherapy researchers seek to understand the mechanisms by which cancer cells evade detection. They are bringing new therapies to market, notably immune checkpoint inhibitors, which help the immune system recognize and target cancer cells as foreign. These therapies are more specific than chemotherapy, which causes damage to many healthy cells. "The way I describe it to my patients is to think about the last time they had a bacterial infection and got really sick," says Dr. Dale Shepard, a medical oncologist at the Cleveland Clinic. "That's an example of a robust immune response." By contrast, some of Shepard's patients have advanced cancers that present with few symptoms. "I see patients all the time that have five-inch tumors that are totally ignored by the immune system." Oncologists like Shepard are cautiously optimistic about the prospects of cancer immunotherapy, as they've seen it work firsthand. Some of the newest treatments, which have been most effective at treating kidney, colon, prostate, and lung cancers, have brought some of Shepard's patients with advanced tumors back from the brink of death. The therapies have even proved tolerable to nonagenarians, like former president Jimmy Carter. But for some patients, such as those with slower-growing cancers, the response has been minimal at best. That said, cancer immunotherapy is not quite a home run yet. The next step for researchers is to better understand why some patients aren't receptive to immunotherapies at all, while others show near-miraculous improvement. Oncologists are also hoping to see new therapies for hematologic cancers, like leukemias and lymphomas. Some 1,500 cancer immunotherapy drugs are currently in the research and development pipeline. Bluestone, who is heading up the Parker Initiative, has already scoped out some near-term research initiatives for the coming year, such as new ways to modify T-cells (the immune system's anti-cancer warriors) to better recognize and kill cancer cells. Additionally, the initiative will provide sophisticated technology to labs such as machines for DNA sequencing. And Bluestone is researching how to apply medical imaging technology, which can offer a three-dimensional picture of tissues and tumors to better understand how these cells communicate with each other. "We want to look deeper than ever before," he says. "We want to identify what cancers come back, and seek out subtle changes in the immune system that we can exploit." Dr. Prateek Mendiratta is a clinical associate of medicine at Duke Cancer Center. He treats patients with cancer every day, and is keeping a watchful eye on developments in the field of immunotherapy. I ask Mendiratta for his thoughts on Sean Parker making a big impact in the space. "Oh wow," he said, seemingly puzzled that a household-name tech billionaire would want to plant a flag in this particular area of research. But on further reflection, Mendiratta came around to the idea of Silicon Valley types investing their time and resources into the space. "We have to keep thinking outside the box," he says. "If more patients can see durable responses and remissions, I'm excited to see people outside of the industry step in." The oncologists I spoke to recognized that physicians desperately need a new set of tools to treat patients. And if an outsider from the tech industry can do it, all power to them. For his part, Parker asks every researcher who wants to get involved about the projects they wish they were doing (a very Silicon Valley question). He says he wants to fund the ideas that have been deemed "too complicated or too ambitious" for the status quo. Shepard is ready for this kind of thinking. "It's a daily frustration for me that traditional chemotherapies don't work as well as we'd like," he says. "I think enough people are willing now to stand up and do the right thing for patients, even if that means changing the way we do things."
PubMed | University Utrecht, UCB Pharma, Copenhagen University, Rheuma Medicus and 4 more.
Type: Clinical Trial, Phase III | Journal: Annals of the rheumatic diseases | Year: 2015
To identify the first time point of an MRI-verified response to certolizumab pegol (CZP) therapy in patients with rheumatoid arthritis (RA).Forty-one patients with active RA despite disease-modifying antirheumatic drug therapy were randomised 2:1 to CZP (CZP loading dose 400mg every 2weeksat weeks 0-4; CZP 200mg every 2weeksat weeks 6-16) or placeboCZP (placebo at weeks 0-2; CZP loading dose at weeks 2-6; CZP 200mg every 2weeks at weeks 8-16). Contrast-enhanced MRI of one hand and wrist was acquired at baseline (week 0) and weeks 1, 2, 4, 8 and 16. All six time points were read simultaneously, blinded to time, using the Outcome Measures in Rheumatology Clinical Trials RA MRI scoring system. Primary outcome was change in synovitis score in the CZP group; secondary outcomes were change in bone oedema (osteitis) and erosion scores and clinical outcome measures.Forty patients were treated (27 CZP, 13 placeboCZP), and 36 (24 CZP, 12 placeboCZP) completed week 16. In the CZP group, there were significant reductions from baseline synovitis (Hodges-Lehmann estimate of median change, -1.5, p=0.049) and osteitis scores (-2.5, p=0.031) at week 16. Numerical, but statistically insignificant, MRI inflammation reductions were observed at weeks 1-2 in the CZP group. No significant change was seen in bone erosion score. Improvements across all clinical outcomes were seen in the CZP group.CZP reduced MRI synovitis and osteitis scores at week 16, despite small sample size and the technical challenge of reading six time points simultaneously. This study provides essential information on optimal MRI timing for subsequent trials.ClinicalTrials.gov, NCT01235598.
News Article | December 14, 2016
Could predictive algorithms be the key to creating a successful cancer vaccine? Two US nonprofit organizations plan to find out by pitting a range of computer programs against each other to see which can best predict a candidate for a personalized vaccine from a patient’s tumour DNA. The Parker Institute for Cancer Immunotherapy in San Francisco, California, and the Cancer Research Institute of New York City announced the algorithmic battle on 1 December. It is part of a multimillion-dollar joint project to solve a major puzzle in the nascent field of cancer immunotherapy: which of a patient’s sometimes hundreds of cancer mutations could serve as a call-to-arms for their immune system to attack their tumours. If the effort succeeds, it could spur the development of personalized cancer vaccines that use fragments of these mutated proteins to fire up the body’s natural immune responses to them. Because these mutations are found in cancer cells and not healthy ones, the hope is that this would provide a non-toxic way to battle tumours. The idea is gaining traction. In 2014, news that vaccines containing such mutated proteins had vanquished tumours in mice set off a mad dash to find out whether the approach would work in people. A generation of biotechnology companies has been founded around the concept, and clinical trials run by academic labs are under way. Still, a challenge remains. To be a good candidate for a vaccine, a mutated cancer protein must be visible to T cells, the soldiers of the immune system. And for that to happen, tumour cells must chew up the protein into fragments. Those fragments then must bind to specialized proteins, which are shipped to the cell’s surface to be displayed to passing T cells. The trick that vaccine researchers must master is using a tumour’s DNA to predict which mutations to home in on. “We can do the sequencing and find out the mutations, but it’s very hard to know which of these tens or hundreds or thousands of mutations are actually going to protect people from the growth of their cancers,” says Pramod Srivastava, an immunologist at the University of Connecticut School of Medicine in Farmington. One approach is to use algorithms to predict which bits of a mutated protein might be seen by a T cell. These work by analysing where the proteins could be cleaved, for example, and which of the resulting fragments will bind tightly to the molecules that put them on display. But each laboratory has a different “secret sauce”, says Robert Schreiber, a cancer immunologist at Washington University in St. Louis, Missouri. And most are not very predictive: Robert Petit, chief scientific officer of biotechnology company Advaxis in Princeton, New Jersey, estimates that the algorithms are typically less than 40% accurate. To solve the problem, the Parker Institute and the Cancer Research Institute launched their challenge. They have arranged for 30 laboratories that already use such algorithms to apply their secret sauces to the same DNA and RNA sequences. The sequences will come from cancers such as melanoma and lung cancer, which tend to have many hundreds of mutations (see ‘Mutation map’) and thus could provide ample possibilities for a vaccine. A handful of other laboratories will then test whether any T cells in the tumour recognize those fragments, and are stimulated by them — a sign of a good vaccine target. The alliance will not publicly announce a winner, but hopes to use the most accurate algorithms to design vaccines for clinical trials. Algorithms can provide a quick answer to a complicated question — crucial if personalized vaccines are to be deployed on a large scale. But ultimately, Srivastava says that the best way to improve the algorithms is to collect more data from animal studies to learn about how T cells naturally respond to mutations. His lab and others are making hundreds of putative vaccines tailored to an individual tumour, and administering them to mice to see which are capable of fighting the cancer. And Drew Pardoll, a cancer immunologist at Johns Hopkins University in Baltimore, Maryland, worries that algorithms may never account for some factors that influence T-cell responses. For example, mutations may be less suitable for a vaccine if they have arisen early in tumour development, giving the immune system time to begin viewing them as ‘normal’. Pardoll argues that the field needs faster, easier and more accurate laboratory tests to determine which mutations best trigger a T-cell response. “We don’t yet know enough about the rules to make perfect predictions,” he says. “You can algorithm until the cows come home and you’re not really going to know if you’re improving things.” But in the absence of speedy lab tests, companies need algorithms, argues Robert Ang, chief business officer at Neon Therapeutics of Cambridge, Massachusetts. “There is already evidence to show that this approach works despite the imperfect algorithms,” he says. “Improving the algorithms even more could be very meaningful.”
News Article | December 1, 2016
SAN FRANCISCO and NEW YORK, Dec. 1, 2016 /PRNewswire/ -- The Parker Institute for Cancer Immunotherapy and the Cancer Research Institute (CRI) today announced a major collaboration focused on neoantigens. The search for these unique cancer markers has become a robust area of research as...
News Article | April 13, 2016
A project to speed development of cancer-fighting drugs that harness the immune system has academic and drug industry researchers collaborating and sharing their findings like never before. The newly created Parker Institute for Cancer Immunotherapy is being funded by a $250 million grant from Sean Parker, the co-founder of the file-sharing site Napster and Facebook's first president. It brings together partners at six top academic cancer centers, dozens of drugmakers and other groups. "Everybody knows that we need to move forward and change the model" for cancer research, Jeffrey Bluestone, an immunology researcher and the institute's CEO, told The Associated Press Tuesday. "The goal here is to rapidly move our discoveries to patients." For decades, fiercely competitive and secretive drugmakers protected their money-making discoveries with patents and lawsuits. Academic researchers likewise often guarded their work closely until it was published because their promotions, awards and sometimes revenue from licensing patents depended on individual achievement. That often slowed progress. With the increasing cost and complexity of research, drugmakers began licensing or buying patents and research programs from university researchers. Then big drugmakers began collaborating with each other and buying smaller companies, to share research costs, speed up the drug development process and get an edge on rivals. The Parker Institute, founded nine months ago, pushes those trends to a new level, by creating a virtual "sandbox" in which scientists at different institutions can work collaboratively, Bluestone said. About 300 scientists at leading cancer institutions - Memorial Sloan Kettering Cancer Center; Stanford Medicine; University of California, Los Angeles; University of California, San Francisco; University of Pennsylvania; and The University of Texas MD Anderson Cancer Center - will share their findings. They'll focus on early research. After initial patient testing, the institute's technology-transfer committee will strike licensing deals with drugmakers best able to develop those drugs, providing funding for other early research. Those drugmakers, from industry giants Amgen Inc. and Pfizer Inc., to small drug and diagnostic test developers, will fund the much-larger tests needed for drug approval, which can include hundreds or thousands of patients and cost hundreds of millions of dollars. Parker worked with hundreds of scientists to create a roadmap for the institute's work. It will quickly fund projects fitting its scientific targets and then rapidly enroll many of the 300,000 or more patients treated at the six centers each year in tests of resulting experimental drugs. "We'll make progress against three or four cancer types in the next several years," Parker predicts. He added that to be most effective, immunotherapy must become an initial treatment. Now it's usually reserved until patients relapse after chemotherapy and other standard treatments that weaken the immune system. Scientists have tried less-sophisticated strategies to use the immune system against cancer for about a century, with limited success, noted Dr. Eric Rubin, head of early stage cancer drug development at Merck & Co. It took recent advances in cell biology, genetics and related science to make progress. Now there are a handful of approved immunotherapy drugs that greatly extend lives of some patients with lung cancer and melanoma. Those include Merck's Keytruda and Bristol-Myers Squibb Co.'s Yervoy and Opdivo. They are so-called "checkpoint inhibitors," which block molecules that slow down or turn off the immune system's ability to attack cancer cells. Other immunotherapy approaches that will be part of the institute's initial work include CAR-T therapy, in which a patient's T-cells are removed from the blood, engineered to be "cancer assassins," then injected into the patient, Parker said. Researchers also will develop therapeutic viruses and vaccines to drive the immune system to recognize and attack tumors. "The Parker Institute does have the potential to accelerate development (of drugs) that will enable a greater number of cures," Rubin said. "We're very happy to be part of this."