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.

Center for Engineering Mechanobiology 2.0: Developing ‘Mechanointelligence’

by Evan Lerner

The dynamics governing mechanointelligence vary greatly along time- and length-scales, so detailed models of individual cells and their components are necessary to connect the effects of their physical environments to the downstream effects those forces have on biological processes.

The National Science Foundation’s Science and Technology Center (STC) program is its flagship funding mechanism for organizing interdisciplinary research on cutting-edge topics. Penn’s Center for Engineering MechanoBiology (CEMB) is one of the 18 active STCs, bringing together dozens of researchers from Penn Engineering and the Perelman School of Medicine, as well as others spread across campus and at partner institutions around the world.

With its NSF funding now renewed for another five years, the Center is entering into a new phase of its mission, centered on the nascent concept of “mechanointelligence.”

Mechanobiology is the study of the physical forces that govern the behavior of cells and their communication with their neighbors. Mechanointelligence adds another layer of complexity, attempting to understand the forces that allow cells to sense, remember and adapt to their environments.

Ultimately, harnessing these forces would allow researchers to help multicellular organisms — plants, animals and humans — better adapt to their environments as well.

“Mechanointelligence is a key element of a cell’s ability to survive and reproduce,” says CEMB Director and Eduardo D. Glandt President’s Distinguished Professor Vivek Shenoy. “Just like with complex organisms, a cell’s ‘fitness’ depends on its environment, and adapting means rewiring how its genes are expressed.”

Read the full story in Penn Engineering Today.

Vivek Shenoy is Eduardo D. Glandt President’s Distinguished Professor in Materials Science and Engineering, Bioengineering and Mechanical Engineering and Applied Mechanics.

César de la Fuente Receives 2022 RSEQ Young Investigator Award

César de la Fuente, PhD

César de la Fuente, Presidential Assistant Professor in Psychiatry, Bioengineering, Microbiology, and in Chemical and Biomolecular Engineering has been honored with a 2022 Young Investigator Award by the Royal Spanish Society of Chemistry (RSEQ) for his pioneering research efforts to combine the power of machines and biology to help prevent, detect, and treat infectious diseases.

Read the RSEQ’s announcement here.

This story originally appeared in Penn Medicine News’s Awards & Accolades post for April 2022.

 

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.

Erin Berlew and Rhea Chitalia Receive Solomon R. Pollack Awards for Excellence in Graduate Bioengineering Research

The Solomon R. Pollack Award for Excellence in Graduate Bioengineering Research is given annually to the most deserving Bioengineering graduate students who have successfully completed research that is original and recognized as being at the forefront of their field. This year Penn Bioengineering recognizes the outstanding work of two graduate students in Bioengineering: Erin Berlew and Rhea Chitalia.

Erin Berlew, Ph.D. candidate in Bioengineering

Erin Berlew is a Ph.D. candidate in the lab of Brian Chow, Associate Professor in Bioengineering. She successfully defended her thesis, titled “Single-component optogenetic tools for cytoskeletal rearrangements,” in December 2021. In her research, she used the BcLOV4 optogenetic platform discovered/developed in the Chow lab to control RhoGTPase signaling. Erin earned a B.S. in Chemistry from Haverford College in 2015 and was an Americorps member with City Year Philadelphia from 2015-2016. “Erin is a world-class bioengineering with an uncommon record of productivity gained through her complementary expertise in molecular, cellular, and computational biology,” says Chow. “She embodies everything wonderful, both academically and culturally, about our graduate program and its distinguished history.” Erin’s hobbies outside the lab include spending time with family, reading mystery novels, enjoying Philadelphia, and crossword puzzles. In the future, she hopes to continue to teach for the BE department (she has already taught ENGR 105 and served as a TA for undergraduate and graduate courses) and to conduct further research at Penn.

Rhea Chitalia, Ph.D. candidate in Bioengineering

Rhea Chitalia is a Ph.D. candidate in Bioengineering and a member of the Computational Biomarker Imaging Group (CBIG), advised by Despina Kontos, Matthew J. Wilson Associate Professor of Research Radiology II in the Perelman School of Medicine. Rhea completed her B.S.E. in Biomedical Engineering at Duke University in 2015. Her doctoral research concerns leveraging machine learning, bioinformatics, and computer vision to develop computational imaging biomarkers for improved precision cancer care. In December 2021 she successfully defended her thesis titled “Computational imaging biomarkers for precision medicine: characterizing intratumor heterogeneity in breast cancer.” “It has been such a privilege to mentor Rhea on her dissertation research,” says Kontos. “Rhea has been a star graduate student. Her work has made fundamental contributions in developing computational methods that will allow us to gain important insight into tumor heterogeneity by utilizing a multi-modality imaging approach.” David Mankoff, Matthew J. Wilson Professor of Research Radiology in the Perelman School of Medicine, served as Rhea’s second thesis advisor. “It was a true pleasure for me to work with Rhea and to Chair her BE Thesis Committee,” Mankoff adds. “Rhea’s Ph.D. thesis and thesis presentation was one of the best I have had the chance to be involved with in my graduate mentoring career.” After graduation, Rhea hopes to further precision medicine initiatives through the use of real world, multi-omic data in translational industry settings. She will be joining Invicro as an Imaging Scientist. In her spare time, Rhea enjoys trying new restaurants, reading, and spending time with friends and family.

 

The Changing Face of Portraiture at Penn

by Katherine Unger Baillie

One of the new portraits in Leidy depicts Jane Hinton, one of the first two Black women to earn a doctorate in veterinary medicine from Penn. Captions on the photos chronicle the achievements of those displayed, but also, in some cases, the challenges they faced due to their race or gender.

A grand split staircase inside the entrance to Leidy Labs invites visitors into the home of the School of Arts & SciencesBiology Department. As students ascend or descend on their way to lab meetings and classes, a set of faces looks down on them—not the old, gilt-framed portraits that long hung in the stairwell, but 14 new photos in chestnut-colored wooden frames, depicting scientists who have close connections to Penn and the department. The gallery now highlights a more diverse suite of individuals, such as Emily Gregory, the first female teaching fellow at Penn, and Roger Arliner Young, the first African American woman to earn a doctorate in zoology.

The new art is part of a collective effort by the department, working with guidance from the University Curator’s office, to rethink how portraiture and representation operate in the halls of their buildings. Many other University departments, schools, and leaders are in the process of undertaking similar initiatives, driven in part by the question: How can the walls of campus buildings better reflect the communities they serve?

“We have about 1,500 to 1,600 portraits in our collection,” says University curator Lynn Marsden-Atlass. “Most of them are paintings by white men of white men. Since I have been the University curator, my goal has really been to bring in more visible diversity to our art collection. And now we’ve been getting increasing numbers of requests, like from the Biology Department, to take on some of this themselves.”

The changes are meant to enhance a sense of inclusion for all at Penn, notably students, says history of art professor Gwendolyn DuBois Shaw. “There are certain contexts that students, in particular, want to assert that they belong,” she says, “that they are not just at Penn, but they’re of Penn.”

Pushing against homogeny

At Penn and many institutions like it, portraits find their way onto walls through a variety of means. Portraits honor department chairs, deans, or others who have ascended to the top ranks of the academy. Sometimes they depict thought leaders in a field, who may or may not have a direct connection to the University. And occasionally donors write into their gift agreement that a portrait will be hung in recognition of their philanthropy.

The result, however, can mean building walls that function like memorials or museums, highlighting the past but not the current community, or a hoped-for future one.

Located at one of the unofficial “entrances” to Penn’s campus at 34th and Walnut streets, the 16-foot-tall bronze form of Brick House, by artist Simone Leigh, makes a statement. Installed in November 2020, it is the first campus sculpture of and by a Black woman.

“I’ve had such an interesting set of conversations about what the walls of Penn are for,” says Dani Bassett, a professor in the School of Engineering and Applied Science. “We as an institution have used the walls to display our history. But there’s a sense in which the students who walk the halls feel that, especially when those faces are not diverse, this kind of art can be really oppressive, saying that, ‘This space is not for me, it’s only for white men.’ So, the question is, how do we venerate our history without hurting our students? Are our walls the place for history or the place for the future?”

In June 2020, amid widespread Black Lives Matter protests, Bassett, together with Junhyong Kim, chair of the Biology Department, as well as other faculty and staff, addressed an open letter requesting institutional and financial support for diversifying portraiture at Penn.

“Many spaces at Penn reflect its history but do not reflect our core values of diversity and inclusion, nor do they accurately reflect the student, staff, and faculty bodies that comprise the Penn of today, or those we envision to comprise the Penn of tomorrow,” they wrote. More than 430 members of the Penn community signed the letter.

Bassett has felt the need to act—and felt it most viscerally—when they interact with students, who have identified the issue of portraiture as an area that makes them feel uncomfortable, even unwelcome. For example, Bassett notes, one room in which students present their thesis proposals (and later defend their Ph.D. theses) is lined with portraits of white men. “The students walk into this room and think, ‘Here is this space where I will be evaluated and I will be evaluated, most likely, by people who are not like me,’” Bassett says. “It was those conversations with students that made me realize this is so important to address.”

Read the full story in Penn Today.

Dani Bassett is the J. Peter Skirkanich Professor, with appointments in the Departments of Bioengineering and Electrical & Systems Engineering in the School of Engineering and Applied Science, the Department of Physics & Astronomy in the School of Arts & Sciences, and the Departments of Neurology and Psychiatry in the Perelman School of Medicine.

 

Herman P. Schwan Distinguished Lecture: “Nucleoside-modified mRNA-LNP therapeutics” (Drew Weissman, Perelman School of Medicine)

We hope you will join us for the Spring 2022 Herman P. Schwan Distinguished Lecture by Dr. Drew Weissman, hosted by the Department of Bioengineering.

Date: Tuesday, March 29, 2022
Time: 3:30-5:00 PM
Location: Bodek Lounge, Houston Hall
Reception to follow
Zoom Link
Password: schwan22

Drew Weissman, M.D., Ph.D.

Speaker: Drew Weissman, M.D., Ph.D.
Roberts Family Professor in Vaccine Research, Department of Medicine
Perelman School of Medicine
University of Pennsylvania

Abstract:

Vaccines prevent 4-5 million deaths a year making them the principal tool of medical intervention worldwide. Nucleoside-modified mRNA was developed over 15 years ago and has become the darling of the COVID-19 pandemic with the first 2 FDA approved vaccines based on it. These vaccines show greater than 90% efficacy and outstanding safety in clinical use. The mechanism for the outstanding immune response induction are the prolonged production of antigen leading to continuous loading of germinal centers and the adjuvant effect of the LNPs, which selectively stimulate T follicular helper cells that drive germinal center responses. Vaccine against many pathogens, including HIV, HCV, HSV2, CMV, universal influenza, coronavirus variants, pancoronavirus, nipah, norovirus, malaria, TB, and many others are currently in development. Nucleoside-modified mRNA is also being developed for therapeutic protein delivery. Clinical trials with mRNA encoded monoclonal antibodies are underway and many other therapeutic or genetic deficient proteins are being developed. Finally, nucleoside-modified mRNA-LNPs are being developed and used for gene therapy. Cas9 knockout to treat transthyretin amyloidosis has shown success in phase 1 trials. We have developed the ability to target specific cells and organs, including lung, brain, heart, CD4+ cells, all T cells, and bone marrow stem cells, with LNPs allowing specific delivery of gene editing and insertion systems to treat diseases such as sickle cell anemia, Nucleoside-modified mRNA will have an enormous potential in the development of new medical therapies.

Bio:

Drew Weissman, M.D., Ph.D. is a professor of Medicine at the Perelman School of Medicine, University of Pennsylvania. He received his graduate degrees from Boston University School of Medicine. Dr. Weissman, in collaboration with Dr. Katalin Karikó, discovered the ability of modified nucleosides in RNA to suppress activation of innate immune sensors and increase the translation of mRNA containing certain modified nucleosides. The nucleoside-modified mRNA-lipid nanoparticle vaccine platform Dr. Weissman’s lab created is used in the first 2 approved COVID-19 vaccines by Pfizer/BioNTech and Moderna. They continue to develop other vaccines that induce potent antibody and T cell responses with mRNA–based vaccines. Dr. Weissman’s lab also develops methods to replace genetically deficient proteins, edit the genome, and specifically target cells and organs with mRNA-LNPs, including lung, heart, brain, CD4+ cells, all T cells, and bone marrow stem cells.

About the Schwan Lecture:

The Herman P. Schwan Distinguished Lecture is in honor of one of the founding members of the Department of Bioengineering, who emigrated from Germany after World War II and helped create the field of bioengineering in the US. It recognizes people with a similar transformative impact on the field of bioengineering.

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

Penn Engineers Secure Wellcome Leap Contract for Lipid Nanoparticle Research Essential in Delivery of RNA Therapies

by Melissa Pappas

The Very Large Scale Microfluidic Integration (VLSMI) platform, a technology developed by the Penn researchers, contains hundreds of mixing channels for mass-producing mRNA-carrying lipid nanoparticles.

Penn Engineering secured a multi-million-dollar contract with Wellcome Leap under the organization’s $60 million RNA Readiness + Response (R3) program, which is jointly funded with the Coalition for Epidemic Preparedness Innovations (CEPI). Penn Engineers aim to create “on-demand” manufacturing technology that can produce a range of RNA-based vaccines.

The Penn Engineering team features Daeyeon Lee, Evan C Thompson Term Chair for Excellence in Teaching and Professor in Chemical and Biomolecular Engineering, Michael Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering, David Issadore, Associate Professor in Bioengineering and Electrical and Systems Engineering, and Sagar Yadavali, a former postdoctoral researcher in the Issadore and Lee labs and now the CEO of InfiniFluidics, a spinoff company based on their research. Drew Weissman of the Perelman School of Medicine, whose foundational research directly continued to the development of mRNA-based COVID-19 vaccines, is also a part of this interdisciplinary team.

The success of these COVID-19 vaccines has inspired a fresh perspective and wave of research funding for RNA therapeutics across a wide range of difficult diseases and health issues. These therapeutics now need to be equitably and efficiently distributed, something currently limited by the inefficient mRNA vaccine manufacturing processes which would rapidly translate technologies from the lab to the clinic.

Read more in Penn Engineering Today.

A Protein Controlled by both Light and Temperature May Open Doors to Understanding Disease-related Cell Signal Pathways

by Melissa Pappas

The brighter edges of the cells in the middle and upper right panels show the optogenetic proteins collecting at the membrane after light exposure. At higher temperatures, however, the proteins become rapidly inactivated and thus do not stay at the membrane, resulting in the duller edges seen in the bottom right panel.

Most organisms have proteins that react to light. Even creatures that don’t have eyes or other visual organs use these proteins to regulate many cellular processes, such as transcription, translation, cell growth and cell survival.

The field of optogenetics relies on such proteins to better understand and manipulate these processes. Using lasers and genetically engineered versions of these naturally occurring proteins, known as probes, researchers can precisely activate and deactivate a variety of cellular pathways, just like flipping a switch.

Now, Penn Engineering researchers have described a new type of optogenetic protein that can be controlled not only by light, but also by temperature, allowing for a higher degree of control in the manipulation of cellular pathways. The research will open new horizons for both basic science and translational research.

Lukasz Bugaj, Bomyi Lim, and Brian Chow

Lukasz Bugaj, Assistant Professor in Bioengineering (BE), Bomyi Lim, Assistant Professor in Chemical and Biomolecular Engineering, Brian Chow, Associate Professor in BE, and graduate students William Benman in Bugaj’s lab, Hao Deng in Lim’s lab, and Erin Berlew and Ivan Kuznetsov in Chow’s lab, published their study in Nature Chemical Biology. Arndt Siekmann, Associate Professor of Cell and Developmental Biology at the Perelman School of Medicine, and Caitlyn Parker, a research technician in his lab, also contributed to this research.

The team’s original aim was to develop a single-component probe that would be able to manipulate specific cellular pathways more efficiently. The model for their probe was a protein called BcLOV4, and through further investigation of this protein’s function, they made a fortuitous discovery: that the protein is controlled by both light and temperature.

Read more in Penn Engineering Today.