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Five Years of Transforming Cancer Immunotherapy Research, Five Promises Kept

How PICI has delivered on its mission five years after launch, and what the future holds

Five years ago, the Parker Institute for Cancer Immunotherapy (PICI) launched with an ambitious vision: bring together a team of the country’s best scientists and clinicians and empower them to work together to solve the toughest problems in cancer research.

Initially backed by a $250 million grant from Silicon Valley entrepreneur and philanthropist Sean Parker, that vision is now a reality.

“We have seen an incredible amount of progress toward the ultimate goal of turning all cancers into curable diseases, and we’ve laid the groundwork for a future that can bring new treatments to patients who are counting on us,” said John Connolly, PhD, Chief Scientific Officer.

Here are five promises PICI made on day one, how we’ve delivered so far and what’s ahead.

Build Unprecedented Collaborations to Solve Cancer’s Toughest Problems

PICI brings the top experts together to do bold research, then we accelerate that work by bringing in the right partners. Through more than 40 active partnerships, PICI has bridged the gap between academia and industry, co-funded novel research, enabled unprecedented data sharing, and streamlined study design and patient accrual on national clinical trials.

From the research institutions that make up PICI’s core academic partners, to nonprofits that share PICI’s mission and values, to biotech and pharmaceutical companies – like Bristol Myers Squibb – working to bring cutting-edge cancer research to life, PICI has fueled collaboration that has changed the field and accelerated breakthrough discoveries.

“We realized early on that since PICI and the Cancer Research Institute share so many of the same goals, we’d be stronger working together than separately,” said Jill O’Donnell-Tormey, PhD, Chief Executive Officer and Director of Scientific Affairs of the Cancer Research Institute (CRI). “In just a few short years, we’re already seeing results, including co-funded studies in pancreatic, prostate and breast cancer, that are helping us answer some of the most difficult questions in immunotherapy research.”

Translate Ideas into Clinical Trials More Quickly Than Anyone Can Alone

Patients don’t have time to wait for science. Instead, they need science to come up with tomorrow’s cures today.

One way to do that is to conduct clinical trials more quickly, especially in diseases like pancreatic cancer, which have proven difficult to treat even with the breakthroughs of modern immunotherapy.

In 2017, PICI and its partners launched a pancreatic cancer trial called PRINCE, which evaluated a combination of chemotherapy, a checkpoint inhibitor and a unique antibody. Enrolling at remarkable speed, researchers presented early results less than two years later at the American Association for Cancer Research Annual Meeting, showing the combination has the ability to shrink tumors. The team published additional data in December 2020. The work is ongoing, but the study’s leaders say it delivers on the promise of speeding innovative trials in tough diseases.

“This truly represents a new model for drug development, with an ability to enroll patients nationally at a faster pace than any institution could alone,” said Robert Vonderheide, MD, DPhil, a PICI investigator, member of the CRI Clinical Accelerator leadership and director of the Abramson Cancer Center of the University of Pennsylvania. “It gives us the ability to be nimble in a way no single investigator can be, while also producing data that is industry-level in its quality.”

The learnings of the PRINCE trial have laid the groundwork for future PICI research, including a new pancreatic cancer trial which will build on these findings. They also prove the promise of PICI’s approach as researchers tackle other disease types like brain tumors, with studies based on work from PICI researcher Hideho Okada, MD, PhD, a Professor of Neurological Surgery at the University of California, San Francisco.

Develop a New Generation of Safer, More Effective T Cell Therapies

In 2019, PICI-supported researchers became the first in the United States to use CRISPR gene editing on cancer cells in humans, a truly historic achievement in the field.

PICI researchers have demonstrated the potential of this technology to treat many diseases that were previously not able to be treated or cured.

The SINATRA trial found genetically editing a cancer patient’s immune cells using CRISPR/Cas9 technology, then infusing those cells back into the patient, appears safe and feasible. The study was initially presented at the 2019 American Society of Hematology Annual Meeting and Exposition, then published in Science in February 2020.

“Our data from the first three patients enrolled in this clinical trial demonstrate two important things that, to our knowledge, no one has ever shown before. First, we can successfully perform multiple edits with precision during manufacturing, with the resulting cells surviving longer in the human body than any previously published data have shown. Second, thus far, these cells have shown a sustained ability to attack and kill tumors,” said Carl June, MD, the Richard W. Vague Professor in Immunotherapy and director of the Center for Cellular Immunotherapies in the Abramson Cancer Center, director of PICI at the Perelman School of Medicine at the University of Pennsylvania, and the study’s senior author.

The work continues to serve as proof-of-concept for future gene editing approaches in the field, including ongoing work within the PICI network. By showing CRISPR/Cas9 technology can target multiple genes at the same time in humans, PICI researchers have demonstrated the potential of this technology to treat many diseases that were previously not able to be treated or cured.

Better Understand Why Immunotherapy Only Works for Some to Improve Outcomes for All

Checkpoint inhibitors have changed the face of cancer care, but not every patient benefits from them. Five years ago, PICI promised to figure out why.

To find the answer, PICI researchers conducted multiple studies comparing responders, non-responders and patients who relapsed. One trial, called AMADEUS, examined when cancer is most vulnerable, potentially creating a “heat map” doctors can use to guide patient treatment in the future. Padmanee Sharma, MD, PhD, a Professor of Genitourinary Medical Oncology and Immunology in the Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center, is leading this work.

Another, called REVIVE, breaks down silos by combining and analyzing data from multiple sources to discover more effective treatments for patients who don’t respond. This work is deepening our understanding of resistance to PD-1 therapy – the most commonly used checkpoint inhibitor – potentially paving the way toward strategies to overcome it.

By working together, we ensure the improvements we make will reach patients more quickly.

The next step is to share what we’re learning with the field in order to shape the path forward. This is where PICI’s model of collaboration proves so effective.

“We brought together leaders from industry, nonprofits and academia to not only spell out the mechanisms of PD-1 resistance, but also to work together on strategies to beat that resistance moving forward,” said Theresa LaVallee, PhD, Vice President, Translational Medicine and Regulatory Affairs. “These are top experts in the field who would likely never have worked together without PICI bringing them to the table.”

By working together, we ensure the improvements we make will reach patients more quickly.

Improve Personalized Cancer Vaccines

Neoantigens, tiny markers that arise from cancer mutations, flag cells as cancerous and could be the key to unlocking a new generation of immunotherapies. Targeting the right neoantigens with a cancer vaccine or a cell therapy has the potential to eliminate a patient’s cancer. The question is, which ones?

To find the answer, PICI and its partners brought together 36 of the top biotech, pharma, university and scientific nonprofit research teams. The idea of the Tumor Neoantigen Selection Alliance (TESLA) wasn’t to pick a winner. It was to help the field understand what makes a good neoantigen candidate, showing us how to target tumors more effectively. The findings published in Cell in October 2020.

“This research has the potential to improve drug makers’ and researchers’ mathematical algorithms. It can prioritize antigens most likely to be present on each patient’s cancer and most visible to the immune system while deprioritizing the ones that aren’t. That means better individualized treatments for patients,” said Lisa Butterfield, PhD, Vice President, Research and Development.

Leading the Future of Cancer Breakthroughs

In addition to delivering on promises from the past, PICI is also focused on the future.

Through its Early Career Researcher Awards, PICI is committed to supporting the brightest rising stars in the field.

With projects like the Cancer Data and Evidence Library (CANDEL) analysis platform, PICI has provided the field with an unparalleled big data analysis tool, helping scientists visualize information and run machine learning models in seconds.

By supporting the creation of new companies based on game changing ideas – like Arsenal Biosciences, a cell therapy manufacturing company focused on solid tumors – PICI is working to ensure the breakthroughs that can help change cancer care will move to the clinic as quickly as possible.

“More than anything else, we set out with a promise to maximize the potential of immunotherapy to give all cancer patients new hope,” said Ute Dugan, MD, PhD, Chief Medical Officer. “We won’t stop until we deliver.”

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