reprinted from Issue 24, Spring 2017 of Frontiers of Medicine (PDF)
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In addition to advancing immunotherapy approaches in the clinic and laboratory, UCSF is now part of an even larger effort to exploit the immune system’s full potential to treat cancer.
In April 2016, UCSF was named one of six major cancer centers – along with Memorial Sloan Kettering Cancer Center, Stanford Medicine, UCLA, the University of Pennsylvania and the University of Texas MD Anderson Cancer Center – to receive support from the Parker Institute for Cancer Immunotherapy. The institute was created by a $250 million gift from the Parker Foundation, a private philan-thropic organization established by Silicon Valley entrepreneur Sean Parker, who is perhaps best known for his roles as founding president of Facebook and co-founder of Napster.
UCSF immunologist Jeffrey A. Bluestone, PhD, A.W. and Mary Margaret Clausen Distinguished Professor, is president and chief executive officer of the entire institute. Lewis Lanier, PhD, chair of the Department of Microbiology and Immunology and holder of the J. Michael Bishop, MD, Distinguished Professorship, directs the UCSF center.
“We wanted to bring three things together: great science, great collaboration, and reduced bureaucracy that allows scientists to get back doing innovative science rather than constantly raising money,” said Bluestone. “We’re trying to bring all these pieces together to ‘hack the system,’ as Sean would say. We want people to take their most adventurous ideas and give them a try.”
Bluestone spent decades investi-gating ways to rein in the immune system to prevent autoimmune diseases such as type 1 diabetes, which develops when the body attacks insulin-producing islet cells in the pancreas. One of the most feared side effects of powerful immunosuppressants is that they may stimulate cancer or infections, as organ transplant patients know all too well. And one of the biggest side effects of amping up the immune system to attack cancer is autoimmunity, including conditions such as diabetes, inflammatory bowel disease and lung inflammation. “My whole career has been about checks and balances, tolerance versus immunity, on versus off,” said Bluestone.
‘A New Way of Doing Science’
As head of the Parker Institute, he now leads a bold enterprise that has made initial investments of $10 million to $15 million in each of the six Parker Institute centers. Collectively, the consortium has also created a common agreement that allows centers to share inventions and discoveries, manage intellectual property and create standardized ways to analyze data, collect tissue samples, and work collectively on clinical trials through a single Institutional Review Board.
The institute also partners with other nonprofits and the pharmaceutical industry to conduct innovative clinical trials – accessing novel and experimental drugs, testing them in combination studies, and using learn-as-you-go approaches to more quickly identify promising prospects. The Parker Institute collaborates with technology companies to bring new tools that are not yet commercially available to the centers, and create new machines specifically engineered to accelerate research.
Perhaps most importantly, the Parker Institute fosters deep partnerships among its six sites, more than 50 laboratories and 350 researchers. “Good collaboration is more than just common ideas and projects,” said Bluestone. “It’s about a sense of trust and collegiality. The best way to do that is to have people interact a lot together.” Their retreats feature a “speed dating with data” component, giving each center five minutes to highlight their most exciting investigations. They also hold monthly lab meetings, the option to share manuscripts when they are submitted to a journal rather than waiting until they are published, and social gatherings at scientific meetings where researchers’ families are welcome.
The Parker Institute is already pursuing ambitious ideas, including a cell therapy clinical trial that takes T cells from patients and uses CRISPR – a new gene-editing technique – to remove one of the immune system brakes and add a T cell receptor that targets a tumor antigen. This combines the power of checkpoint inhibitors with T cell therapy. “It’s highly risky, because you’re taking off the brakes on the cell, but we’re doing our best to do it in a very safe way,” said Bluestone. “We’ve invested millions of dollars for this trial, and it’s not something that would be easily done through an NIH [National Institutes of Health] grant.”
“The Parker Institute is a new way of doing science that’s incredibly powerful,” said Alan Ashworth, the The UCSF Helen Diller Family Comprehensive Cancer Center president. “The idea that you partner major institutions and leading scientists with access to resources without all the administrative burden of very complicated grant application procedures is the thing of the future.”
“We need science that’s high-risk and making big bets, but we also need administrative structures that are willing to take risks,” said Bluestone. “Does that mean we could fail? Sure, but I’d love to take a chance of being great rather than average in perpetuity.”