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.

 

2022 Graduate Research Fellowships for Bioengineering Students

Congratulations to the two Bioengineering students to receive 2022 National Science Foundation Graduate Research Fellowship Program (NSF GRFP) fellowships. The prestigious NSF GRFP program recognizes and supports outstanding graduate students in NSF-supported fields. The eighteen Penn 2022 honorees were selected from a highly-competitive pool of over 12,000 applications nationwide. Further information about the program can be found on the NSF website.

 Gianna Therese Busch, PhD student, Bioengineering
Gianna is a member of the systems biology lab of Arjun Raj, Professor in Bioengineering and Genetics. Her research focuses on single-cell differences in cancer metabolism and drug resistance.

 

 

 

Shawn Kang, BSE/MSE, Bioengineering (’22)
Shawn conducted research in the BIOLines Lab of Dan Huh, Associate Professor in Bioengineering, where he worked to develop more physiologically relevant models of human health and disease by combining organs-on-a-chip and organoid technology.

 

 

 

The following Bioengineering students also received Honorable Mentions:
Michael Steven DiStefano, PhD student
Rohan Dipak Patel, PhD student
Abraham Joseph Waldman, PhD student

Read the full list of NSF GRFP Honorees on the Grad Center at Penn website.

Penn Engineers Develop a New Method that Could Enable a Patient’s Own Antibodies to Eliminate Their Tumors

Tsourkas
Andrew Tsourkas, Ph.D.

One of the reasons that cancer is notoriously difficult to treat is that it can look very different for each patient. As a result, most targeted therapies only work for a fraction of cancer patients. In many cases, patients will have tumors with no known markers that can be targeted, creating an incredible challenge in identifying effective treatments. A new study seeks to address this problem with the development of a simple methodology to help differentiate tumors from healthy, normal tissues.

This new study, published in Science Advances, was led by Andrew Tsourkas, Professor in Bioengineering and Co-Director of the Center for Targeted Therapeutics and Translational Nanomedicine (CT3N), who had what he describes as a “crazy idea” to use a patient’s antibodies to find and treat their own tumors, taking advantage of the immune system’s innate ability to identify tumors as foreign. This study, spearheaded by Burcin Altun, a former postdoctoral researcher in Tsourkas’s lab, and continued and completed by Fabiana Zappala, a former graduate student in Penn Bioengineering, details their new method for site-specifically labeling “off-the-shelf” and native serum autoantibodies with T cell–redirecting domains.

Researchers have known for some time that cancer patients will generate an antibody response to their own tumors. These anti-tumor antibodies are quite sophisticated in their ability to specifically identify cancer cells; however, they are not sufficiently potent to confer a therapeutic effect. In this study, Tsourkas’s team converted these antibodies into bispecific antibodies, thereby increasing their potency. T cell-redirecting bispecific antibodies are a new form of targeted therapeutic that forms a bridge between tumor cells and T cells which have been found to be as much as a thousand-times more potent than antibodies alone. By combining the specificity of a patient’s own antibodies with the potency of bispecific antibodies, researchers can effectively create a truly personalized therapeutic that is effective against tumors.

In order to test out this new targeted therapeutic approach, the Tsourkas lab had to develop an entirely new technology, allowing them to precisely label antibodies with T cell targeting domains, creating a highly homogeneous product.  Previously it has not been possible to convert native antibodies into bispecific antibodies, but Tsourkas’s Targeted Imaging Therapeutics and Nanomedicine or TITAN lab specializes in the creation of novel targeted imaging and therapeutic agents for detection and treatment of various diseases. “Much is yet to be done before this could be considered a practical clinical approach,” says Tsourkas. “But I hope at the very least this works stimulates new ideas in the way we think about personalized medicine.”

In their next phase, Tsourkas’s team will be working to separate anti-tumor antibodies from other antibodies found in patients’ serum (which could potentially redirect the bispecific antibodies to other locations in the body), as well as examining possible adverse reactions or unintended effects and immunogenicity caused by the treatment. However, this study is just the beginning of a promising new targeted therapeutic approach to cancer treatment.

This work was supported by Emerson Collective and the National Institutes of Health, National Cancer Institute (R01 CA241661).

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.

Vijay Balasubramanian Discusses Theoretical Physics in Quanta Magazine

Cathy and Marc Lasry Professor Vijay Balasubramanian at Penn’s BioPond.

In an interview with Quanta Magazine, Vijay Balasubramanian discusses his work as a theoretical physicist, noting his study of the foundations of physics and the fundamentals of space and time. He speaks of the importance of interdisciplinary study and about how literature and the humanities can contextualize scientific exploration in the study of physics, computer science, and neuroscience.

Balasubramanian is Cathy and Marc Lasry Professor in the Department of Physics and Astronomy in the Penn School of Arts and Sciences and a member of the Penn Bioengineering Graduate Group.

Read “Pondering the Bits That Build Space-Time and Brains” in Quanta Magazine.

Bioengineering Graduate Jason Andrechak Wins Graduate Leadership Award

Jason Andrechak

Congratulations to recent Penn Bioengineering graduate Jason Andrechak on winning a Graduate Leadership Awards for 2022. Each year a select number of students across the university are recognized for their service and lasting contributions to graduate student life at Penn. Andrechak, one of only ten recipients in 2022, won a Dr. Andy Binns Award for Outstanding Service to Graduate and Professional Student Life. This award is presented to “graduate or professional students, upon their graduation from Penn, who have significantly impacted graduate and professional student life through service involvement in student life initiatives or organizations.” Andrechak won this award for his “service and leadership in advocating for equity and accessibility during the transition to virtual operations and following a period of leadership transition within the Graduate and Professional Student Assembly (GAPSA). ”

Andrechak completed his Ph.D. in Bioengineering in 2022, where he studied macrophage immunotherapy in solid tumors in the lab of Dennis E. Discher, Robert D. Bent Professor in Chemical and Biomolecular Engineering, Bioengineering, and Mechanical Engineering and Applied Mechanics. He was named a National Science Foundation Graduate Research Fellow in 2018. He has actively led the Graduate Association of Bioengineers (GABE) as Community Service & Outreach chair from 2017-2019 and as co-President from 2019-2022. He also served as the Director of Equity & Access for the Graduate & Professional Student Assembly (GAPSA) from 2020-2021, in addition to several other service and advisory roles at the department, school, and university levels.

Learn more about the Penn Graduate Leadership Awards and read the full list of recipients on the Grad Center at Penn website.

2022 Penn Engineering Senior Design Project Competition Winners Announced

by Ebonee Johnson

Each year, Penn Engineering’s seniors present their Senior Design projects, a year-long effort that challenges them to test and develop solutions to real-world problems, to their individual departments. The top three projects from each department go on to compete in the annual Senior Design Competition, sponsored by the Engineering Alumni Society, which involves pitching projects to a panel of judges who evaluate their potential in the market.

This year’s panel included 42 judges, 21 in-person and 21 online, who weighed in on 18 projects. Each winning team received a $2,000 prize, generously sponsored by Penn Engineering alumnus Kerry Wisnosky.

This year, Bioengineering teams won two of the four interdepartmental awards.

Technology & Innovation Award

This award recognized the team whose project represents the highest and best use of technology and innovation to leverage engineering principles.

Team Modulo Prosthetics with Vijay Kumar, Dean of Penn Engineering, and Lyle Brunhofer, Chair of the 2022 Senior Design Competition Committee.

Winner: Team Modulo Prosthetics
Department: Bioengineering
Team Members: Alisha Agarwal, Michelle Kwon, Gary Lin, Ian Ong, Zachary Spalding
Mentor: Michael Hast
Instructors: Sevile Mannickarottu, David Meaney, Michael Siedlik
Abstract: Modulo Prosthetic is an adjustable, low-cost, thumb prosthetic with integrated haptic feedback that attaches to the metacarpophalangeal (MCP) joint of partial hand amputees and assists in activities of daily living (ADLs).

Leadership Award

This award recognizes the team which most professionally and persuasively presents their group project to incorporate a full analysis of their project’s scope, advantages and challenges, as well as addresses the research’s future potential and prospects for commercialization.

Team ReiniSpec with Vijay Kumar, Dean of Penn Engineering, and Lyle Brunhofer, Chair of the 2022 Senior Design Competition Committee.

Winner: Team ReiniSpec
Department: Bioengineering
Team Members: Caitlin Frazee, Caroline Kavanagh, Ifeoluwa Popoola, Alexa Rybicki, Michelle White
Mentor: JeongInn Park
Instructors: Sevile Mannickarottu, David Meaney, Michael Siedlik
Abstract: ReiniSpec is a redesigned speculum to improve the gynecological exam experience, increasing patient comfort with a silicone shell and using motorized arm adjustments to make it easily adjustable for each patient, while also incorporating a camera, lights, and machine learning to aid in better diagnosis by gynecologists.

Read the full list of competition winners in Penn Engineering Today.

 The 2022 Senior Design Competition Committee was chaired by Lyle Brunhofer, Penn Engineering Alumni Society Board Member and alumnus of Penn Bioengineering (BSE 2014, Master’s 2015).

Work for these and all Bioengineering senior design projects was conducted in the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace, the primary teaching lab for the Department of Bioengineering. Learn more about all eleven 2022 senior design projects in Bioengineering here.

2022 Penn Bioengineering Senior Design Teams Win Multiple Accolades

After a year of hybrid learning, Penn Bioengineering (BE) seniors were excited to return to the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace for Senior Design (BE 495 & 496), a two-semester course in which students work in teams to conceive, design and pitch their capstone projects in bioengineering. This year’s projects include tools for monitoring health, software to improve communication for the healthcare and supply chain industries, and devices to improve patient care for women and underrepresented minorities.

The year culminated in the annual Senior Design Expo on April 13 in the Singh Center for Nanotechnology, in which the students presented their pitches to a panel of alumni judges, followed by demonstrations in the George H. Stephenson  Foundation Educational Laboratory & Bio-MakerSpace which were open to the entire Penn community. This year’s winners of the Bioengineering Senior Design Competition were teams Chrysalis, Modulo Prosthetics, and ReiniSpec.

Team 11 (ReiniSpec) From L to R: Ifeoluwa Popoola, Alexa Rybicki, JeongInn Park (TA), Caitlin Frazee, Michelle White, Caroline Kavanagh (on laptop).

The three winning teams went on to compete in the annual interdepartmental Senior Design Competition sponsored by the Penn Engineering Alumni Society. BE took home two of the four interdepartmental awards: Team Modulo Prosthetics won the “Technology and Innovation Prize,” recognizing the project which best represents the highest and best use of technology and innovation to leverage engineering principles; and Team ReiniSpec won the “Leadership Prize,” which recognizes the team which most professionally and persuasively presents their group project to incorporate a full analysis of their project scope, advantages, and challenges, and addresses the commercialization and future potential of their research.

All BE teams were also required to submit their projects to local and national competitions, and were met with resounding success. “The creativity and accomplishment of this Senior Design class is really unparalleled,” said David Meaney, Solomon R. Pollack Professor in Bioengineering, Senior Associate Dean of Penn Engineering, and instructor for Senior Design. “The number of accolades received by these students, as well as the interest in transforming their ideas into real products for patients, reached a new level that makes us extremely proud.”

Keep reading for a full list of this year’s projects and awards.

Team 1 – MEViD

MEViD (Multichannel Electrochemical Viral Diagnostic) is a modular, low cost device that leverages electrochemistry to rapidly diagnose viral diseases from saliva samples.

Team members: Yuzheng (George) Feng, Daphne Kontogiorgos-Heintz, Carisa Shah, Pranshu Suri, & Rachel Zoneraich

Team 2 – MOD EZ-IO

MOD EZ-IO is a low-cost, novel intraosseous drill that uses force and RPM readings to alert the user via an LED when they have breached cortical bone and entered cancellous bone, guiding proper IO placement.

Team members: Gregory Glova, Kaiser Okyan, Patrick Paglia, Rohan Vemu, & Tshepo Yane

Team 3 – Harvest by Grapevine

Harvest by Grapevine is a user-centric software solution that merges social network communication and supply chain logistics to connect hospitals and suppliers under one unified platform.

Team members: Nicole Bedanova, Kerry Blatney, Blake Grimes, Brenner Maull, & Lukas Yancopoulos

Team 4 – CliniCall

CliniCall helps streamline and centralize communication channels, offering a real-time monitoring device that enables on-site/attending physicians to communicate with on-call physicians through a livestream of patients and data.

Team members: Neepa Gupta, Santoshi Kandula, Sue Yun Lee, & Ronil Synghal

Team 5 – PneuSonus

PneuSonus is a low-cost, user-friendly wearable strap that aids in detecting pediatric pneumonia by using frequency analysis of sound waves transmitted through the lungs to identify specific properties related to fluid presence, a valid indicator specific to pneumonia.

Team members: Iman Hossain, Kelly Lopez, Sophia Mark, Simi Serfati, & Nicole Wojnowski

Team 6 – Chrysalis

Chrysalis is a smart swaddle system comprising an electric swaddle and accompanying iOS application that comforts neonatal abstinence syndrome infants via stochastic resonance and maternal heartbeat vibrational patterns to reduce opioid withdrawal symptoms without pharmacological intervention or constant nurse oversight as well as streamlines the Eat, Sleep, Console documentation process for nurses.

Team members: Julia Dunn, Rachel Gu, Julia Lasater, & Carolyn Zhang

Team 7 – EquitOx

EquitOx is a revolutionized fingertip pulse oximeter designed for EMS that addresses racial inequality in medicine through the use of one-off tongue-calibrated SpO2 measurements.

Team members: Ronak Bhagia, Estelle Burkhardt, Juliette Hooper, Caroline Smith, & Kevin Zhao

Team 8 – Modulo Prosthetics

Modulo Prosthetic is an adjustable, low-cost, thumb prosthetic with integrated haptic feedback that attaches to the metacarpophalangeal (MCP) joint of partial hand amputees and assists in activities of daily living (ADLs).

Team members: Alisha Agarwal, Michelle Kwon, Gary Lin, Ian Ong, & Zachary Spalding

Team 9 – Cor-Assist By Cygno Technologies

COR-ASSIST by Cygno Technologies is a low-cost intra-aortic balloon enhancement that directly supports heart function by increasing cardiac output to 2.8L/min, at a much lower cost and bleeding risk than the current Impella cardiac assist device.

Team members: Francesca Cimino, Allen Gan, Shawn Kang, Kristina Khaw, & William Zhang

Team 10 – Pedalytics

Pedalytics Footwear is a rechargeable sandal that continuously monitors foot health and prevents diabetic foot ulcer formation by novelly tracking three key metrics indicative of ulceration, temperature, oxygen saturation, and pressure, and sending alerts to patients via the Pedalytics app when metric abnormalities are detected.

Team members: Samantha Brosler, Constantine Constantinidis, Quincy Hendricks, Ananyaa Kumar, & María José Suárez

Team 11 – ReiniSpec

ReiniSpec is a redesigned speculum to improve the gynecological exam experience, increasing patient comfort with a silicone shell and using motorized arm adjustments to make it easily adjustable for each patient, while also incorporating a camera, lights, and machine learning to aid in better diagnosis by gynecologists.

Team members: Caitlin Frazee, Caroline Kavanagh, Ifeoluwa Popoola, Alexa Rybicki, & Michelle White

Learn more about the 2022 Senior Design projects, including full abstracts and photo gallery, on the Stephenson Bio-MakerSpace website.

Watch all the 2022 project pitches on the BE Labs Youtube channel 2022 Senior Design Playlist: