CAR T Cell Therapy Reaches Beyond Cancer

Penn Medicine researchers laud the early results for CAR T therapy in lupus patients, which point to broader horizons for the use of personalized cellular therapies.

Penn Medicine’s Carl June and Daniel Baker.

Engineered immune cells, known as CAR T cells, have shown the world what personalized immunotherapies can do to fight blood cancers. Now, investigators have reported highly promising early results for CAR T therapy in a small set of patients with the autoimmune disease lupus. Penn Medicine CAR T pioneer Carl June and Daniel Baker, a doctoral student in cell and molecular biology in the Perelman School of Medicine, discuss this development in a commentary published in Cell.

“We’ve always known that in principle, CAR T therapies could have broad applications, and it’s very encouraging to see early evidence that this promise is now being realized,” says June, who is the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine at Penn Medicine and director of the Center for Cellular Immunotherapies at the Abramson Cancer Center.

T cells are among the immune system’s most powerful weapons. They can bind to, and kill, other cells they recognize as valid targets, including virus-infected cells. CAR T cells are T cells that have been redirected, through genetic engineering, to efficiently kill specifically defined cell types.

CAR T therapies are created out of each patient’s own cells—collected from the patient’s blood, and then engineered and multiplied in the lab before being reinfused into the patient as a “living drug.” The first CAR T therapy, Kymriah, was developed by June and his team at Penn Medicine, and received Food & Drug Administration approval in 2017. There are now six FDA-approved CAR T cell therapies in the United States, for six different cancers.

From the start of CAR T research, experts believed that T cells could be engineered to fight many conditions other than B cell cancers. Dozens of research teams around the world, including teams at Penn Medicine and biotech spinoffs who are working to develop effective treatments from Penn-developed personalized cellular therapy constructs, are examining these potential new applications. Researchers say lupus is an obvious choice for CAR T therapy because it too is driven by B cells, and thus experimental CAR T therapies against it can employ existing anti-B-cell designs. B cells are the immune system’s antibody-producing cells, and, in lupus, B cells arise that attack the patient’s own organs and tissues.

This story is by Meagan Raeke. Read more at Penn Medicine News.

Carl June is a member of the Penn Bioengineering Graduate Group. Read more stories featuring June’s research here.

FDA Approves Penn Pioneered CAR T Cell Therapy for Third Indication

The U.S. Food and Drug Administration has expanded its approval for Kymriah, a personalized cellular therapy developed at the Abramson Cancer Center, this time for the treatment of adults with relapsed/refractory follicular lymphoma who have received at least two lines of systemic therapy. “Patients with follicular lymphoma who relapse or don’t respond to treatment have a poor prognosis and may face a series of treatment options without a meaningful, lasting response,” said Stephen J. Schuster, the Robert and Margarita Louis-Dreyfus Professor in Chronic Lymphocytic Leukemia and Lymphoma in the Division of Hematology Oncology. It’s the third FDA approval for the “living drug,” which was the first of its kind to be approved, in 2017, and remains the only CAR T cell therapy approved for both adult and pediatric patients.

“In just over a decade, we have moved from treating the very first patients with CAR T cell therapy and seeing them live healthy lives beyond cancer to having three FDA-approved uses of these living drugs which have helped thousands of patients across the globe,” said Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in Penn’s Perelman School of Medicine and director of the Center for Cellular Immunotherapies in the Abramson Cancer Center and director of the Parker Institute for Cancer Immunotherapy at Penn. “Today’s news is new fuel for our work to define the future of cell therapy and set new standards in harnessing the immune system to treat cancer.”

Research from June, a member of the Penn Bioengineering Graduate Group, led to the initial FDA approval for the CAR T therapy (sold by Novartis as Kymriah) for treating acute lymphoblastic leukemia (ALL), one of the most common childhood cancers.

Read the full announcement in Penn Medicine News.

Penn Anti-Cancer Engineering Center Will Delve Into the Disease’s Physical Fundamentals

by Evan Lerner

A colorized microscope image of an osteosarcoma shows how cellular fibers can transfer physical force between neighboring nuclei, influencing genes. The Penn Anti-Cancer Engineering Center will study such forces, looking for mechanisms that could lead to new treatments or preventative therapies.

Advances in cell and molecular technologies are revolutionizing the treatment of cancer, with faster detection, targeted therapies and, in some cases, the ability to permanently retrain a patient’s own immune system to destroy malignant cells.

However, there are fundamental forces and associated challenges that determine how cancer grows and spreads. The pathological genes that give rise to tumors are regulated in part by a cell’s microenvironment, meaning that the physical push and pull of neighboring cells play a role alongside the chemical signals passed within and between them.

The Penn Anti-Cancer Engineering Center (PACE) will bring diverse research groups from the School of Engineering and Applied Science together with labs in the School of Arts & Sciences and the Perelman School of Medicine to understand these physical forces, leveraging their insights to develop new types of treatments and preventative therapies.

Supported by a series of grants from the NIH’s National Cancer Institute, the PACE Center is Penn’s new hub within the Physical Sciences in Oncology Network. It will draw upon Penn’s ecosystem of related research, including faculty members from the Abramson Cancer Center, Center for Targeted Therapeutics and Translational Nanomedicine, Center for Soft and Living Matter, Institute for Regenerative Medicine, Institute for Immunology and Center for Genome Integrity.

Dennis Discher and Ravi Radhakrishnan

The Center’s founding members are Dennis Discher, Robert D. Bent Professor with appointments in the Departments of Chemical and Biomolecular Engineering (CBE), Bioengineering (BE) and Mechanical Engineering and Applied Mechanics (MEAM), and Ravi Radhakrishnan, Professor and chair of BE with an appointment in CBE.

Discher, an expert in mechanobiology and in delivery of cells and nanoparticles to solid tumors, and Radhakrishnan, an expert on modeling physical forces that influence binding events, have long collaborated within the Physical Sciences in Oncology Network. This large network of physical scientists and engineers focuses on cancer mechanisms and develops new tools and trainee opportunities shared across the U.S. and around the world.

Lukasz Bugaj, Alex Hughes, Jenny Jiang, Bomyi Lim, Jennifer Lukes and Vivek Shenoy (Clockwise from upper left).

Additional Engineering faculty with growing efforts in the new Center include Lukasz Bugaj, Alex Hughes and Jenny Jiang (BE), Bomyi Lim (CBE), Jennifer Lukes (MEAM) and Vivek Shenoy (Materials Science and Engineering).

Among the PACE Center’s initial research efforts are studies of the genetic and immune mechanisms associated with whether a tumor is solid or liquid and investigations into how physical stresses influence cell signaling.

Originally posted in Penn Engineering Today.

Carl June Receives the Sanford Lorraine Cross Award

Carl June, MD

Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in the Perelman School of Medicine at the University of Pennsylvania, director of the Center for Cellular Immunotherapies at Penn’s Abramson Cancer Center, and member of the Penn Bioengineering Graduate Group, received the $1 million Sanford Lorraine Cross Award for his groundbreaking work in developing chimeric antigen receptor (CAR) T cell therapy. June is a world renowned cancer cell therapy pioneer.

“Sanford Health, the only health system in the country to award a $1 million prize for achievements in the medical sciences, announced the award on April 13 at a special ceremony in Sioux Falls, South Dakota. The biennial award recognizes life-changing breakthroughs and bringing emerging transformative medical innovations to patients.

‘This is a well-deserved and exciting award for one of Penn’s most distinguished faculty members, whose pioneering research has reshaped the fight against cancer and brought fresh hope for both adults and children with the disease,’ said J. Larry Jameson, MD, PhD, Executive Vice President of the University of Pennsylvania for the Health System and Dean of the Perelman School of Medicine. ‘His contributions truly have been transformative for patients across the globe and taken the field of oncology in new and powerful directions.'”

Read the full story in Penn Medicine News.

Alumni Spotlight: Danielle Rossi

Danielle Rossi (M.S.E. 2018)

Danielle Rossi earned her M.S.E. in Bioengineering in December 2018 and is now a R&D Leadership and Development Program Engineer with Johnson & Johnson Medical Devices. Here she reminisces about her research opportunities at Penn and her fond memories of Philly.

“When I first started at Penn, I was amazed by all of the opportunities to learn, to challenge myself, to network, and to innovate. My time at Penn was filled with interesting classes, dedicated faculty, challenging problems to solve, and collaboration. From writing a mock NIH research grant for a tissue engineered Intervertebral Disk in BE 553, to designing an electromechanical device controlled with muscle movement in BE 570, to writing up a business plan and pitching to investors in EAS 546, every new day came with a new venture.

On top of the exciting classes and projects, Penn has numerous research labs and healthcare facilities so that students can apply their skills to real-world problems. While I was a student, I had the opportunity to work at the Abramson Cancer Center in the Cancer Risk Evaluation Program. The program focused on patient risk evaluations, including genetic testing for certain cancers such as breast, ovarian, and sarcoma. This exposed me to the healthcare environment and gave me a new perspective on preemptive medicine.

During my free time, I loved to tour the historically and culturally rich city of Philadelphia. I have the fondest memories of exploring the city with my BE friends and storming the Philly streets when the Eagles won the Super Bowl!

While at Penn, I was sure to utilize Career Services to help me spruce up my resume and interview skills. I was lucky enough to meet with Johnson & Johnson Medical Devices at a Penn career fair and was offered a spot in the R&D Leadership and Development Program. The program allows me to rotate through three different J&J Medical Device companies as an R&D Engineer to gain exposure to new product development, mechanical design, computational modeling, manufacturing, design quality and more. ”

This post is part of BE’s Alumni Spotlight series. Read more testimonies from BE Alumni on the BE website.