What were the chances? Captivated by a fencing demonstration at his elementary school in St. Louis, MO, an American-born son of French parentage went straight home and announced his desire to learn the sport. Meanwhile, an internationally recognized fencer, who had once coached the Egyptian National team, had settled in St. Louis and was busy making plans to establish a fencing club there. Two dreams collided: The Fencers Academy of St. Louis took shape and the boy learned to fence, and to fence well. Meet Alexandre Amice (BSE’20, MSE’20).
Amice’s passion for the sport remained strong throughout high school, and the year he walked on to the Penn Fencing Team as a freshman engineering student, he was voted by the captains and coaches as Most Dedicated Fencer.
Of the three types of fencing swords: the épée, the foil and the sabre, Amice’s weapon of choice is the light and flexible foil. In foil bouts, the target area for scoring touches is limited to the torso, requiring the fencers to remain closely engaged and in constant motion. Amice characterizes his fencing style as “athletic,” with his build and skillset well-matched with his weapon.
Amice cites his measured and deliberate competition strategy as useful in his intellectual life. As he concurrently works toward his undergraduate degree in electrical engineering and mathematics and a master’s in robotics, Amice clearly is not one to waste energy.
THE COOL ONE
The sabre is the weapon of choice for Penn World Scholar and freshman electrical engineering major, Enzo Bergamo. At an early age, he determined the discipline of sabre fencing to be “the cool one,” with its reputation for quickness, aggression, slashing touches and split-second decision making. Compared in speed and spirit to Formula 1 racing by Olympic sabre fencer Daryl Homer, the target area for the discipline is the entire torso, the head, and the arms up to the wrist.
Andy Ma, Penn’s head fencing coach, also serves as sabre coach, and Bergamo feels fortunate to be able to work with him one-on-one in lessons once or twice a week. After twelve years of high-level fencing in Sao Paulo, Brazil, Bergamo attributes his renewed love for the sport to Ma’s influence and attentive demeanor. For Bergamo, being able to face down frustration and maintain physical and emotional balance are valuable attributes, with or without a sword in his hand.
Bergamo notes that he and his teammates are known as “student athletes,” not “athlete students,” and, with an electrical engineering concentration in data science and a minor in computer and information science, he envisions a master’s degree in his future. Bergamo’s overarching goal, he states, is “making a positive impact in my home country.”
SMALL BUT MIGHTY
At 5’3,” Kristina Khaw, a sophomore bioengineering major, fences with the épée, the largest and heaviest of fencing swords. Bouts in épée have been described as “aggressive defensive,” and points can be scored with touches anywhere on the body. Fencers train especially hard to perfect their skills in counter moves.
Obeying her mother’s directive to put her books aside in favor of exercise now and again, Khaw followed her sister, Kathryn (ENG’19), onto the fencing strip. She admits that, as a seventh grader, her greatest incentive to take up the sport was watching Kathryn delightedly stab their cousin with impunity in club practice.
As Khaw describes it, the muscle memory to succeed in épée came easily to her. Her stats provide proof: From the USA Fencing Nationals in the summer of her high school sophomore year, Khaw brought back to her Plainsboro, NJ, home the title of Division ll Women’s Épée Champion. Other notable wins and honors followed.
Khaw is a problem solver by nature and believes that her strategizing as a fencer creates new brain connections, enhancing her ability to think about things in new ways. Accordingly, she finds myriad applications of her athletic training to her life as a Penn Engineer.
“One touch at a time” is Khaw’s fencing mantra and, as she continues her studies on the pre-med track, her calm and logic will undoubtedly inform her journey.
The prestigious NSF GRFP program recognizes and supports outstanding graduate students in NSF-supported fields. Further information about the program can be found on the NSF website. BE is thrilled to congratulate our excellent students on these well-deserved accolades! Continue reading below for a list of 2020 recipients and descriptions of their research.
William Benman is a Ph.D. student in the lab of Assistant Professor of Bioengineering, Lukasz Bugaj. His work in the Bugaj lab focuses on developing novel optogenetic tools to control and study cell function.
Paul Gehret is a Ph.D. student and Ashton Fellow in the lab of Riccardo Gottardi, Assistant Professor of Pediatrics at the Perelman School of Medicine. Paul works on pediatric cartilage and airway tissue engineering for children with subglottic stenosis. He and his team apply classic tissue engineering principles to the airway.
Rebecca Haley is a Ph.D. student in the lab of Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering. Her current project aims to use polymer and/or lipid nanoparticles for the intracellular delivery of proteins. Successful delivery of proteins (such as antibodies) in this fashion may allow for targeting of previously undruggable intracellular targets.
Patrick John Mulcahey is a Research Assistant and Graduate Student in the Children’s Hospital of Philadelphia (CHOP) Epilepsy Research Lab of Douglas A. Coulter, Professor of Pediatrics at the Perelman School of Medicine. His work focuses on developing techniques that combine electrophysiology with two-photon excitation microscopy to study a potential biomarker of the seizure onset zone in models of drug-refractory epilepsy.
Catherine Porter is a Ph.D. student in the lab of Alex J. Hughes, Assistant Professor of Bioengineering. She is working on developing high-throughput methods to produce and characterize human-cell-derived kidney organoids for disease modeling and genetic screening. Currently, she is focused on engineering physicochemical control to improve organoid homogeneity.
Sarah Shepherd is a Ph.D. student who is co-advised in the Michael J. Mitchell lab and the lab of David Issadore, Associate Professor of Bioengineering and Electrical and Systems Engineering (ESE). Her research aims to combine microfabrication with biomaterial design of lipid nanoparticles to address major shortcomings in the field of nanomedicine. Currently, she is prototyping a scale-up microfluidic device to produce lipid nanoparticles for gene therapy.
In response to the unprecedented challenges presented by the global outbreak of the novel coronavirus SARS-CoV-2, Penn Bioengineering’s faculty, students, and staff are finding innovative ways of pivoting their research and academic projects to contribute to the fight against COVID-19. Though these projects are all works in progress, I think it is vitally important to keep those in our broader communities informed of the critical contributions our people are making. Whether adapting current research to focus on COVID-19, investing time, technology, and equipment to help health care infrastructure, or creating new outreach and educational programs for students, I am incredibly proud of the way Penn Bioengineering is making a difference. I invite you to read more about our ongoing projects below.
Novel Chest X-Ray Contrast
David Cormode, Associate Professor of Radiology and Bioengineering
The Cormode and Noel labs are working to develop dark-field X-ray imaging, which may prove very helpful for COVID patients. It involves fabricating diffusers that incorporate gold nanoparticles to modify the X-ray beam. This method gives excellent images of lung structure. Chest X-ray is being used on the front lines for COVID patients, and this could potentially be an easy to implement modification of existing X-ray systems. The additional data give insight into the health state of the microstructures (alveoli) in the lung. This new contrast mechanics could be an early insight into the disease status of COVID-19 patients. For more on this research, see Cormode and Noel’s chapter in the forthcoming volume Spectral, Photon Counting Computed Tomography: Technology and Applications, edited by Katsuyuki Taguchi, Ira Blevis, and Krzysztof Iniewski (Routledge 2020).
Computational Models for Targeting Acute Respiratory Distress Syndrome (ARDS). The severe forms of COVID-19 infections resulting in death proceeds by the propagation of the acute respiratory distress syndrome or ARDS. In ARDS, the lungs fill up with fluid preventing oxygenation and effective delivery of therapeutics through the inhalation route. To overcome this major limitation, delivery of antiinflammatory drugs through the vasculature (IV injection) is a better approach; however, the high injected dose required can lead to toxicity. A group of undergraduate and postdoctoral researchers in the Radhakrishnan Lab (Emma Glass, Christina Eng, Samaneh Farokhirad, and Sreeja Kandy) are developing a computational model that can design drug-filled nanoparticles and target them to the inflamed lung regions. The model combines different length-scales, (namely, pharmacodynamic factors at the organ scale, hydrodynamic and transport factors in the tissue scale, and nanoparticle-cell interaction at the subcellular scale), into one integrated framework. This targeted approach can significantly decrease the required dose for combating ARDS. This project is done in collaboration with Clinical Scientist Dr. Jacob Brenner, who is an attending ER Physician in Penn Medicine. This research is adapted from prior findings published in Volume 13, Issue 4 of Nanomedicine: Nanotechnology, Biology and Medicine: “Mechanisms that determine nanocarrier targeting to healthy versus inflamed lung regions” (May 2017).
Sydney Shaffer, Assistant Professor of Bioengineering and Pathology and Laboratory Medicine
Arjun Raj, David Issadore, and Sydney Shaffer are working on developing an integrated, rapid point-of-care diagnostic for SARS-CoV-2 using single molecule RNA FISH. The platform currently in development uses sequence specific fluorescent probes that bind to the viral RNA when it is present. The fluorescent probes are detected using a iPhone compatible point-of-care reader device that determines whether the specimen is infected or uninfected. As the entire assay takes less than 10 minutes and can be performed with minimal equipment, we envision that this platform could ultimately be used for screening for active COVID19 at doctors’ offices and testing sites. Support for this project will come from a recently-announced IRM Collaborative Research Grant from the Institute of Regenerative Medicine with matching funding provided by the Departments of Bioengineering and Pathology and Laboratory Medicine in the Perelman School of Medicine (PSOM) (PI’s: Sydney Shaffer, Sara Cherry, Ophir Shalem, Arjun Raj). This research is adapted from findings published in the journal Lab on a Chip: “Multiplexed detection of viral infections using rapid in situ RNA analysis on a chip” (Issue 15, 2015). See also United States Provisional Patent Application Serial No. 14/900,494 (2014): “Methods for rapid ribonucleic acid fluorescence in situ hybridization” (Inventors: Raj A., Shaffer S.M., Issadore D.).
HEALTH CARE INFRASTRUCTURE
Penn Health-Tech Coronavirus COVID-19 Collaborations
Brian Litt, Professor of Bioengineering, Neurology, and Neurosurgery
In his role as one of the faculty directors for Penn Health-Tech, Professor Brian Litt is working closely with me to facilitate all the rapid response team initiatives, and in helping to garner support the center and remove obstacles. These projects include ramping up ventilator capacity and fabrication of ventilator parts, the creation of point-of-care ultrasounds and diagnostic testing, evaluating processes of PPE decontamination, and more. Visit the Penn Health-Tech coronavirus website to learn more, get involved with an existing team, or submit a new idea.
Dr. Maltese is rapidly developing a low-cost ventilator that could be deployed in Penn Medicine for the expected surge, and any surge in subsequent waves. This design is currently under consideration by the FDA for Emergency Use Authorization (EUA). This example is one of several designs considered by Penn Medicine in dealing with the patient surge.
David F. Meaney, Solomon R. Pollack Professor of Bioengineering and Senior Associate Dean
Led by David Meaney, Kevin Turner, Peter Bruno and Mark Yim, the face shield team at Penn Health-Tech is working on developing thousands of rapidly producible shields to protect and prolong the usage of Personal Protective Equipment (PPE). Learn more about Penn Health-Tech’s initiatives and apply to get involved here.
Update 4/29/20: The Penn Engineering community has sprung into action over the course of the past few weeks in response to COVID-19. Dr. Meaney shared his perspective on those efforts and the ones that will come online as the pandemic continues to unfold. Read the full post on the Penn Engineering blog.
OUTREACH & EDUCATION
Student Community Building
Yale Cohen, Professor of Otorhinolaryngology, Department of Psychology, BE Graduate Group Member, and BE Graduate Chair
Yale Cohen, and Penn Bioengineering’s Graduate Chair, is working with Penn faculty and peer institutions across the country to identify intellectually engaging and/or community-building activities for Bioengineering students. While those ideas are in progress, he has also worked with BE Department Chair Ravi Radhakrishnan and Undergraduate Chair Andrew Tsourkas to set up a dedicated Penn Bioengineering slack channel open to all Penn Bioengineering Undergrads, Master’s and Doctoral Students, and Postdocs as well as faculty and staff. It has already become an enjoyable place for the Penn BE community to connect and share ideas, articles, and funny memes.
Undergraduate Course: Biotechnology, Immunology, Vaccines and COVID-19 (ENGR 35)
Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor of Bioengineering and Chemical and Biomolecular Engineering
This Summer Session II, Professor Dan Hammer and CBE Senior Lecturer Miriam R. Wattenbarger will teach a brand-new course introducing Penn undergraduates to a basic understanding of biological systems, immunology, viruses, and vaccines. This course will start with the fundamentals of biotechnology, and no prior knowledge of biotechnology is necessary. Some chemistry is needed to understand how biological systems work. The course will cover basic concepts in biotechnology, including DNA, RNA, the Central Dogma, proteins, recombinant DNA technology, polymerase chain reaction, DNA sequencing, the functioning of the immune system, acquired vs. innate immunity, viruses (including HIV, influenza, adenovirus, and coronavirus), gene therapy, CRISPR-Cas9 editing, drug discovery, types of pharmaceuticals (including small molecule inhibitors and monoclonal antibodies), vaccines, clinical trials. Some quantitative principles will be used to quantifying the strength of binding, calculate the dynamics of enzymes, writing and solving simple epidemiological models, methods for making and purifying drugs and vaccines. The course will end with specific case study of coronavirus pandemic, types of drugs proposed and their mechanism of action, and vaccine development.
Update 4/29/20: Read the Penn Engineering blog post on this course published April 27, 2020.
Konrad Kording, Penn Integrates Knowledge University Professor of Bioengineering, Neuroscience, and Computer and Information Science
Dr. Kording facilitated Neuromatch 2020, a large virtual neurosciences conferences consisting of over 3,000 registrants. All of the conference talk videos are archived on the conference website and Dr. Kording has blogged about what he learned in the course of running a large conference entirely online. Based on the success of Neuromatch 1.0, the team are now working on planning Neuromatch 2.0, which will take place in May 2020. Dr. Kording is also working on facilitating the transition of neuroscience communication into the online space, including a weekly social (#neurodrinking) with both US and EU versions.
Konrad Kording, Penn Integrates Knowledge University Professor of Bioengineering, Neuroscience, and Computer and Information Science
Dr. Kording is working to launch the Neuromatch Academy, an open, online, 3-week intensive tutorial-based computational neuroscience training event (July 13-31, 2020). Participants from undergraduate to professors as well as industry are welcome. The Neuromatch Academy will introduce traditional and emerging computational neuroscience tools, their complementarity, and what they can tell us about the brain. A main focus is not just on using the techniques, but on understanding how they relate to biological questions. The school will be Python-based making use of Google Colab. The Academy will also include professional development / meta-science, model interpretation, and networking sessions. The goal is to give participants the computational background needed to do research in neuroscience. Interested participants can learn more and apply here.
Journal of Biomedical Engineering Call for Review Articles
Beth Winkelstein, Vice Provost for Education and Eduardo D. Glandt President’s Distinguished Professor of Bioengineering
The American Society of Medical Engineers’ (ASME) Journal of Biomechanical Engineering (JBME), of which Dr. Winkelstein is an Editor, has put out a call for review articles by trainees for a special issue of the journal. The call was made in March 2020 when many labs were ramping down, and trainees began refocusing on review articles and remote work. This call continues the JBME’s long history of supporting junior faculty and trainees and promoting their intellectual contributions during challenging times.
Update 4/29/20: CFP for the special 2021 issue here.
Are you a Penn Bioengineering community member involved in a coronavirus-related project? Let us know! Please reach out to firstname.lastname@example.org.
The Office of the Provost awards the Penn Prize for Excellence in Teaching by Graduate Students in recognition of their profound impact on education across the University. Nominations come directly from undergraduate and graduate students in their courses and are narrowed down to ten awardees each year.
Muir has served as a teaching assistant for coursework in Biomaterials with Skirkanich Assistant Professor of Innovation Michael Mitchell and Tissue Engineering with Robert D. Bent Professor Jason Burdick. She is conducting her thesis on granular hydrogels for musculoskeletal tissue repair under Burdick’s advisement. Muir has also received both NSF and Tau Beta Pi Fellowships for her graduate studies.
Almost every engineering school in the country offers a course in mechatronics — the overlap of mechanical, electrical, and computer engineering in electromechanical system design — but how many offer a course in biomechatronics? Taught by LeAnn Dourte, Ph.D., a Practice Associate Professor in Bioengineering, Penn Engineering’s Biomechatronics course (BE 570) gives students the chance to think about how the principles of mechatronic design can be used in biological settings involving orthopaedics, cardiovascular systems, and respiration, to name a few.
Throughout the course, students engage in different projects related to circuitry, signal processing, mechanics, motors, and analog controls, eventually applying all of these to biological examples before working on a final culminating project in design teams of two. In a simulation meant to mimic the sort of thinking and design processes that go behind innovations in robotic surgery, students create an electromechanical device that acts as a robotic hand. The catch? The “hand” has to have enough dexterity to pick up a water bead with a slipperiness similar to that of human tissue.
In addition to successfully performing this mechanical task using skills that the students learned throughout the semester, design teams also have to incorporate biological interfaces into the final project, such as using EMG signals to move part of the robotic hand, to give one example. Furthermore, each team needs to have a unique element to their design, whether in the use of a second biological interface, the application of Bluetooth to the system, or even a physical extension of the robotic hand to include the electromechanical equivalents of a shoulder, elbow, or wrist joint.
Students Carolyn Godone and Mike Furr (both M.S.E. in Bioengineering ‘19) created a design inspired by the mechanical iris of a camera lens, using gears to push 3-D printed slices together in a symmetrical pattern to close around an object for pickup. They controlled their unique gripper with a thermal sensing camera that could employ a heat map of the device’s user to rotate, raise, and lower the gripper. Another pair of students, Omar Abdoun (BE M.D./Ph.D. student) and Andrew Chan (M.S.E. in Robotics ‘19), made what they called a “cryogripper”: a tissue moistened with water that freezes on demand when it contacts its target hydrogel. The ice allows the target to be lifted without falling, and the tissue can later be thawed with pumps of warm water to release hydrogel.
Spencer Glantz, a graduate of the Penn Bioengineering doctoral program and former member of the Brian Chow Lab, was mentioned in a recent WHYY piece highlighting the efforts of Penn labs to develop rapid, at-home testing for COVID-19. Glantz is currently a co-leader of the molecular biology team for 4Catalyzer, a medical device incubator founded by National Medal of Technology and Innovation recipient, and sponsor of the annual Rothberg Catalyzer Makerthon competition, Jonathan Rothberg. 4Catalyzer is developing the testing technology while Penn researchers are working to evaluate its effectiveness.
Melanie Hilman was born to be a Biomedical Engineer. The daughter of an electrical engineering father and physician mother, Melanie was inspired by her parents work and is now pursuing the intersection of their two careers: bioengineering.
Her passion for engineering began long before Melanie stepped onto Smith Walk.
“I always really loved math and science as a middle school and high school student,” Melanie says.
Melanie quickly discovered that Penn was the perfect place for her. After visiting campus as a prospective student, Melanie knew that she wanted to attend a research-driven university where innovation and discovery was at the top of the curriculum.
“Being in a place so rich with research and really smart minds motivated me to apply here and be a part of this program,” Melanie remembers.
On top of her bioengineering research, Melanie submatriculated into Mechanical Engineering and Applied Mechanics with a focus on Mechanics of Materials because she wants to develop a deep foundation in the mathematical concepts. After gaining this experience, Melanie hopes to conduct complex research and eventually pursue a PhD.
BETWEEN TWO WORLDS
“I really like thinking about the interface between biology and today’s technologies,” Melanie comments. Right now, she’s focused on doing research but she is interested in, one day, developing biomedical technologies for the start-up industry.
As if building the future of bioengineering weren’t enough for Melanie, she is a dedicated member of the Penn community outside of the lab. Throughout her time at Penn, Melanie is a student leader of Penn Hillel, a devoted performer in the Penn Symphony Orchestra and Penn Chamber Music, and a multimedia staff member of the Daily Pennsylvanian. Even when school is out of session, Melanie represents Penn during Alternative Spring Break trips where she took on a leadership position renovating houses in West Virginia. All of this extracurricular work is important to Melanie, as she says these experiences have given her a valuable perspective to carry with her through academic, professional and personal life.
“It makes me feel really fortunate for my upbringing and my experiences,” Melanie shares.
WOMEN IN STEM
When asked about her favorite part of being at Penn Engineering, Melanie was certain about her answer: empowered women engineers.
“Having a really strong female engineering network is super valuable to me,” Melanie says.
Melanie says she’s found friendship and support among her fellow women engineers and that working with women is as fun as it is enriching. While Penn Engineering has proved itself to be an inclusive space for Melanie and others, current research shows that only 13% of professional engineers are women, and, among them, biomedical engineering ranks fourth in terms of career path of women engineers. Faced with these jarring numbers, Melanie is even more committed to encouraging other women to join her in STEM.
Most of all, she is grateful for the community she has found on campus.
“I know I’m going to have a good group of friends after I graduate. I have found other women that I hope to have lasting friendships with.”
Armed with friends and research partners, Melanie Hillman may very well turn the tides for women in engineering and usher in a new era of women in the lab who lead the charge for biomedical innovation.
The George H. Stephenson Foundation Educational Laboratory and Bio-MakerSpace, more commonly known as the Bio-MakerSpace, has recently become a hub for Penn student start-ups that continue after graduation. Beyond offering a home base for projects by Bioengineering majors, the lab is also open to Penn students, regardless of major. Unlike other departmental undergraduate labs, the Bio-MakerSpace encourages interdisciplinary projects and collaborations from students across all different majors.
Even better, the lab has a neutral policy when it comes to intellectual property (IP), meaning all IP behind student projects belongs to the students instead of the lab or the engineering school. With a wide variety of prototyping equipment, coding and software programs installed on lab computers, and an extremely helpful lab staff, the Bio-MakerSpace provides students of all academic backgrounds the resources to turn their ideas into realities or even businesses, as a recent succession of start-ups founded in the lab has shown.
One of the most successful start-ups to come out of the Bio-MakerSpace in the last few years is Group K Diagnostics, founded by 2017 Bioengineering alumna Brianna Wronko. The company focuses on the use of a point-of-care diagnostic device called KromaHealthTM. Offering a variety of different tests based on the input of a small amount of blood, serum, or urine, the device induces a color change through a series of reactions that can be detected through image processing. Developed in part from Wronko’s senior design project (hence the name “Group K”) and in part from her experience working at an HIV clinic, Group K Diagnostics looks to expand access to care for all populations.
But not all start-ups from the Bio-MakerSpace have origins in senior design projects. Three start-ups from 2019, two of which won the Penn President’s Innovation Prize, all began as independent initiatives from students. InstaHub, founded by 2019 Wharton alumnus Michael Wong with help from Bioengineering doctoral candidate Dayo Adewole, is a company that focuses on the use of snap-on automation for light energy conservation. A simple and easy-to-install device with motion and occupancy sensors, InstaHub aims to reduce energy consumption in a way that’s simpler and cheaper than rewiring projects that might otherwise be required. Here, Adewole shares the way that access to the Bio-MakerSpace provided InstaHub with a helpful platform.
The second start-up from 2019 to come out of the Bio-MakerSpace and win a President’s Innovation Prize is Strella Biotechnology, founded by recent graduate Katherine Sizov (Biology 2019). In developing sensors with the ability to detect ethylene gas emitted by rotting fruits, Strella hopes to reduce the immense amount of food waste due to produce simply going bad in storage. With a patent-pending biosensor that mimics the way ripe fruits detect ethylene emissions of nearby rotting fruits, the technology behind Strella involves both biology and aspects of engineering. In this video, Sizov herself talks about the way that the Bio-MakerSpace opened its doors to her, and allowed her work to really take off with the help of resources she wouldn’t have easily found otherwise.
Yet another start-up to use the Bio-MakerSpace as a launch pad for innovation is BioAlert Technologies, comprised of a group of Penn engineering undergraduate and graduate students, including 2019 Bioengineering alumnus Johnny Forde and current Biotechnology student Marc Rosenberg, who is the startup’s CEO and founder. BioAlert’s innovations are in what they call continuous infection monitoring (CIM) systems, designed to detect infections in patients with diabetic foot ulcers. Often, even when properly bandaged by a doctor, these ulcers run the risk of bacterial infection once a patient returns home and continues to care for the wound. BioAlert uses their platform to assess whether or not a bacterial infection might occur in a given patient’s wound, and uses an app to alert both patients and doctors of it, so that patients can receive the proper response treatment and medication as quickly as possible.
Though each of these start-ups used the resources of the Bio-MakerSpace, they are each interdisciplinary approaches to solving real-world problems today. Paired with other student resources at Penn like courses offered under an Engineering Entrepreneurship minor, knowledge from the nearby Wharton business school professors, and competitions like the Rothberg Catalyzer, the Bio-MakerSpace allows for any student to transform their idea into a reality, and potentially take it to market.
New cancer immunotherapies involve extracting a patient’s T cells and genetically engineering them so they will recognize and attack tumors. This type of therapy is not without challenges, however. Engineering a patient’s T cells is laborious and expensive. And when successful, the alterations to the immune system immediately make patients very sick for a short period of time, with symptoms including fever, nausea and neurological effects.
Now, Penn researchers have demonstrated a new engineering technique that, because it is less toxic to the T cells, could enable a different mechanism for altering the way they recognize cancer, and could have fewer side effects for patients.
The technique involves ferrying messenger RNA (mRNA) across the T cell’s membrane via a lipid-based nanoparticle, rather than using a modified HIV virus to rewrite the cell’s DNA. Using the former approach would be preferable, as it only confers a temporary change to the patient’s immune system, but the current standard method for getting mRNA past the cell membrane can be too toxic to use on the limited number of T cells that can be extracted from a patient.
The researchers demonstrated their technique in a study published in the journal Nano Letters. It was led by Michael Mitchell, Skirkanich Assistant Professor of Innovation of bioengineering in the School of Engineering and Applied Science, and Margaret Billingsley, a graduate student in his lab.
They collaborated with one of the pioneers of CAR T therapy: Carl June, the Richard W. Vague Professor in Immunotherapy and director of the Center for Cellular Immunotherapies in the Abramson Cancer Center and the director of the Parker Institute for Cancer Immunotherapy at the Perelman School of Medicine.