2022 Career Award Recipient: Michael Mitchell

by Melissa Pappas

Michael Mitchell (Illustration by Melissa Pappas)

Michael Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, is one of this year’s recipients of the National Science Foundation’s CAREER Award. The award is given to early-career faculty researchers who demonstrate the potential to be role models in their field and invest in the outreach and education of their work.

Mitchell’s award will fund research on techniques for “immunoengineering” macrophages. By providing new instructions to these cells via nanoparticles laden with mRNA and DNA sequences, the immune system could be trained to target and eliminate solid tumors. The award will also support graduate students and postdoctoral fellows in his lab over the next five years.

The project aligns with Mitchell’s larger research goals and the current explosion of interest in therapies that use mRNA, thanks to the technological breakthroughs that enabled the development of COVID-19 vaccines.

“The development of the COVID vaccine using mRNA has opened doors for other cell therapies,” says Mitchell. “The high-priority area of research that we are focusing on is oncological therapies, and there are multiple applications for mRNA engineering in the fight against cancer.”

A new wave of remarkably effective cancer treatments incorporates chimeric antigen receptor T-cell (CAR-T) therapy. There, a patient’s T-cells, a type of white blood cell that fights infections, are genetically engineered to identify, target and kill individual cancer cells that accumulate in the circulatory system.

However, despite CART-T therapy’s success in treating certain blood cancers, the approach is not effective against cancers that form solid tumors. Because T-cells are not able to penetrate tumors’ fibrous barriers, Mitchell and his colleagues have turned to another part of the immune system for help.

Read the full story in Penn Engineering Today.

Penn Medicine CAR T Therapy Expert Carl June Receives 2022 Keio Medical Science Prize

by Brandon Lausch

The award from Japan’s oldest private university honors outstanding contributions to medicine and life sciences.

Richard W. Vague Professor in Immunotherapy Carl June.

Carl June, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in the Perelman School of Medicine and director of the Center for Cellular Immunotherapies at Penn’s Abramson Cancer Center, has been named a 2022 Keio Medical Science Prize Laureate. He is recognized for his pioneering role in the development of CAR T cell therapy for cancer, which uses modified versions of patients’ own immune cells to attack their cancer.

The Keio Medical Science Prize is an annual award endowed by Keio University, Japan’s oldest private university, which recognizes researchers who have made an outstanding contribution to the fields of medicine or the life sciences. It is the only prize of its kind awarded by a Japanese university, and eight laureates of this prize have later won the Nobel Prize. Now in its 27th year, the prize encourages the expansion of researcher networks throughout the world and contributes to the well-being of humankind.

“Dr. June exemplifies the spirit of curiosity and fortitude that make Penn home to so many ‘firsts’ in science and medicine,” said Penn President Liz Magill. “His work provides hope to cancer patients and their families across the world, and inspiration to our global community of physicians and scientists who are working to develop the next generation of treatments and cures for diseases of all kinds.”

Read the full story in Penn Today.

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

Penn Startup Vittoria Biotherapeutics Raises $10M in Seed Funding

Marco Ruella, MD

A Philadelphia life sciences company spun out of Penn is emerging from stealth mode with nearly $10 million from a seed funding round. Vittoria Biotherapeutics’ mission is to overcome limitations of CAR T cell therapy by using unique cell engineering and gene editing technologies to create new therapies that address unmet clinical needs. The technology the company is attempting to commercialize was developed by Marco Ruella, M.D., Assistant Professor of Medicine in the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group, who is the company’s scientific founder.

Read “Penn spinout Vittoria Biotherapeutics emerges from stealth mode with $10M seed round” in the Philadelphia Business Journal.

Penn Medicine and Children’s Hospital of Philadelphia Announce Partnership with Costa Rica for CAR T Cell Therapy

Carl June, MD

Carl June, MD, Professor in the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group, was quoted in a recent press release  announcing a new international partnership between Penn Medicine (PSOM), the Children’s Hospital of Pennsylvania (CHOP), and Costa Rica’s CCSS, or the Caja Costarricense de Seguro Social (Social Security Program), to develop CAR T research in Costa Rica. June is a world renowned cancer cell therapy pioneer whose research led to the initial development and FDA approval of CAR T cell therapy:

“‘At least 15,000 patients across the world have received CAR T cells, and dozens more clinical trials using this approach are in progress, for almost every major tumor type, but people in many parts of the globe still do not have access to treatment with these transformative therapies,’ said Carl H. June, MD, the Richard W. Vague Professor in Immunotherapy and director of the Center for Cellular Immunotherapies in Penn’s Perelman School of Medicine. “We are honored to work with our colleagues in Costa Rica in hopes of building a path for patients in underserved areas to have the opportunity to benefit from clinical research programs offering this personalized therapy.’”

Read the the announcement in Penn Medicine News.

 

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.

Exploring the History of CAR-T Cell Therapy

Carl June, MD

A new feature in Chemistry World explores the history of CAR (chimeric antigen receptor)-T cell therapy, a revolutionary type of therapeutic treatment for certain types of cancer. One of the pioneers of CAR-T cell therapy is Carl June, Richard W. Vague Professor in Immunotherapy in the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group. His groundbreaking research opened the door for FDA approval of the CAR T therapy called Kymriah, which treats acute lymphoblastic leukemia (ALL), one of the most common childhood cancers.

Read “A decade of CAR-T cell therapy” in Chemistry World.

Decade-long Remission After CAR T Cell Therapy

Bill Ludwig, left, was the first patient to receive CAR T cells as part of clinical trials at Abramson Cancer Center. Carl June, right, has played a pioneering roll in the therapeutic use of CAR T cells. (Image: Penn Medicine)

Carl H. June, the Richard W. Vague Professor in Immunotherapy in Pathology and Laboratory Medicine at Penn Medicine, director of the Center for Cellular Immunotherapies and the Parker Institute for Cancer Immunotherapy, and member of the Penn Bioengineering Graduate Group at the University of Pennsylvania, has led a new analytical study published in Nature that explains the longest persistence of CAR T cell therapy recorded to date against chronic lymphocytic leukemia (CLL), and shows that the CAR T cells remained detectable at least a decade after infusion, with sustained remission in both patients. June’s pioneering work in gene therapy led to the FDA approval for the CAR T therapy (sold by Novartis as Kymriah) for treating leukemia and transforming the fight against cancer. His lab develops new forms of T cell based therapies.

Read the story in Penn Today

New Lipid Nanoparticles Improve mRNA Delivery for Engineering CAR T Cells

by Melissa Pappas

The Penn researchers’ latest paper on the design of lipid nanoparticles was featured on the cover of the most recent edition of the journal Nano Letters.

From COVID vaccines to cancer immunotherapies to the potential for correcting developmental disorders in utero, mRNA-based approaches are a promising tool in the fight against a wide range of diseases. These treatments all depend on providing a patient’s cells with genetic instructions for custom proteins and other small molecules, meaning that getting those instructions inside the target cells is of critical importance.

The current delivery method of choice uses lipid nanoparticles (LNPs). Thanks to surfaces customized with binding and signaling molecules, they encapsulate mRNA sequences and smuggle them through the cell membrane. But with a practically unlimited number of variables in the makeup of those surfaces and molecules, figuring out how to design the most effective LNP is a fundamental challenge.

Now, in a study featured on the cover of the journal Nano Letters, researchers from the University of Pennsylvania’s School of Engineering and Applied Science and Perelman School of Medicine have now shown how to computationally optimize the design of these delivery vehicles.

Using an established methodology for comparing a wide range of variables known as “orthogonal design of experiments,” the researchers simultaneously tested 256 candidate LNPs. They found the frontrunner was three times better at delivering mRNA sequences into T cells than the current standard LNP formulation for mRNA delivery.

The study was led by Michael Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering in Penn’s School of Engineering and Applied Science, and Margaret Billingsley, a graduate student in his lab.

Read the full story in Penn Engineering Today.

Penn Bioengineering Celebrates Five Researchers on Highly Cited Researchers 2021 List

The Department of Bioengineering is proud to announce that five of our faculty have been named on the annual Highly Cited Researchers™ 2021 list from Clarivate:

Dani Bassett, Ph.D.

Dani S. Bassett, J. Peter Skirkanich Professor in Bioengineering and in Electrical and Systems Engineering
Bassett runs the Complex Systems lab which tackles problems at the intersection of science, engineering, and medicine using systems-level approaches, exploring fields such as curiosity, dynamic networks in neuroscience, and psychiatric disease. They are a pioneer in the emerging field of network science which combines mathematics, physics, biology and systems engineering to better understand how the overall shape of connections between individual neurons influences cognitive traits.

Robert D. Bent Chair
Jason Burdick, Ph.D.

Jason A. Burdick, Robert D. Bent Professor in Bioengineering
Burdick runs the Polymeric Biomaterials Laboratory which develops polymer networks for fundamental and applied studies with biomedical applications with a specific emphasis on tissue regeneration and drug delivery. The specific targets of his research include: scaffolding for cartilage regeneration, controlling stem cell differentiation through material signals, electrospinning and 3D printing for scaffold fabrication, and injectable hydrogels for therapies after a heart attack.

César de la Fuente, Ph.D.

César de la Fuente, Presidential Assistant Professor in Bioengineering and Chemical & Biomedical Engineering in Penn Engineering and in Microbiology and Psychiatry in the Perelman School of Medicine
De la Fuente runs the Machine Biology Group which combines the power of machines and biology to prevent, detect, and treat infectious diseases. He pioneered the development of the first antibiotic designed by a computer with efficacy in animals, designed algorithms for antibiotic discovery, and invented rapid low-cost diagnostics for COVID-19 and other infections.

Carl June, M.D.

Carl H. June, Richard W. Vague Professor in Immunotherapy in the Perelman School of Medicine and member of the Bioengineering Graduate Group
June is the Director for the Center for Cellular Immunotherapies and the Parker Institute for Cancer Therapy and runs the June Lab which develops new forms of T cell based therapies. June’s pioneering research in gene therapy led to the FDA approval for CAR T therapy for treating acute lymphoblastic leukemia (ALL), one of the most common childhood cancers.

Vivek Shenoy, Ph.D.

Vivek Shenoy, Eduardo D. Glandt President’s Distinguished Professor in Bioengineering, Mechanical Engineering and Applied Mechanics (MEAM), and in Materials Science and Engineering (MSE)
Shenoy runs the Theoretical Mechanobiology and Materials Lab which develops theoretical concepts and numerical principles for understanding engineering and biological systems. His analytical methods and multiscale modeling techniques gain insight into a myriad of problems in materials science and biomechanics.

The highly anticipated annual list identifies researchers who demonstrated significant influence in their chosen field or fields through the publication of multiple highly cited papers during the last decade. Their names are drawn from the publications that rank in the top 1% by citations for field and publication year in the Web of Science™ citation index.

Bassett and Burdick were both on the Highly Cited Researchers list in 2019 and 2020.

The methodology that determines the “who’s who” of influential researchers draws on the data and analysis performed by bibliometric experts and data scientists at the Institute for Scientific Information™ at Clarivate. It also uses the tallies to identify the countries and research institutions where these scientific elite are based.

David Pendlebury, Senior Citation Analyst at the Institute for Scientific Information at Clarivate, said: “In the race for knowledge, it is human capital that is fundamental and this list identifies and celebrates exceptional individual researchers who are having a great impact on the research community as measured by the rate at which their work is being cited by others.”

The full 2021 Highly Cited Researchers list and executive summary can be found online here.

Carl June Highlighted for Success in Gene Therapy

Carl June, MD

Scientific American recently featured two gene therapies that were invented at Penn, including research from Carl June, MD, the Richard W. Vague Professor in Immunotherapy in Pathology and Laboratory Medicine, director of the Center for Cellular Immunotherapies, and member of the Penn Bioengineering Graduate Group, which led to the 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 “Four Success Stories in Gene Therapy” in Scientific American.