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Philanthropy Powering Science: $1.6M in New Funding for Wistar Coronavirus Research

Written by The Wistar Institute on . Posted in Featured News.

In mere weeks, philanthropic support of Wistar’s Coronavirus Discovery Fund has exceeded $1.6M in new funding thanks to an extraordinary response from individuals, foundations, and corporate sponsors. As our scientists focused their research to advance vaccines, drugs, and diagnostics targeting the novel coronavirus, SARS-CoV-2, Wistar donors moved with the same speed, committing to put our discovery science into action in a variety of important ways. This pace of investment in research now underway at Wistar will allow us to accelerate and potentiate progress against SARS-CoV-2 and future viral threats the world may confront.

Under the leadership of Dr. David Weiner, executive vice president, director of the Vaccine & Immunotherapy Center (VIC), and W.W. Smith Charitable Trust Professor in Cancer Research, our team continues to carry out pivotal laboratory testing of its synthetic DNA vaccine. Funding support has enabled us to expand that research through the purchase of critical equipment that allows for real-time, high-throughput assays required for vaccine development, and will hasten the Institute’s ability to respond to future pandemic threats as they arise.

Dr. Daniel Kulp, associate professor in the VIC, is engineering nanoparticle-based immunotherapies that target SARs-CoV-2. He and his team use extremely small (nano) particles to display multiple copies of critical parts of the virus in order to stimulate immunity against COVID-19.  Donor support for his project is allowing the lab to design molecular simulations of the SARS-CoV-2 spike protein — the surface protein that lets the virus invade healthy cells.

Not only did individual donors make a strong commitment to Wistar Science; so did foundations, including The G. Harold and Leila Y. Mathers Charitable Foundation. Dr. Hildegund Ertl, vaccine expert and a professor in the VIC, is creating a SARS-CoV-2 vaccine based on safe viral delivery technologies. Genetically modified adenoviruses are great delivery vehicles for vaccines because they induce neutralizing antibodies and killer T-cell responses. Dr. Ertl’s goal is to apply innovative technologies created in her lab to develop a vaccine that will produce strong and sustained protection to COVID-19. The Mathers Foundation and steadfast Wistar supporters quickly mobilized to provide critical support for this project.

This is not Wistar’s first pandemic. We are uniquely prepared for this moment by a near-century’s worth of Wistar achievement in developing vaccines that have saved countless lives. Wistar’s community of supporters has provided the resources and tools our scientists need to work efficiently and effectively to address this pandemic. For that, we thank you deeply. We’re all in this for science. Because Wistar Science saves lives.

If you would like to play a role in advancing Wistar’s research fighting COVID-19, your donation will keep the momentum going and inspire our scientists to continue tackling the world’s biggest threats. 

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Spotlight on Wistar COVID-19 Researcher: Hildegund C.J. Ertl, M.D. 

Written by The Wistar Institute on . Posted in Featured News.

Dr. Ertl is a global leader in Wistar’s Vaccine & Immunotherapy Center whose research focuses on preventing rabies, HBV, HIV, HPV, influenza, and other deadly viruses using innovative patented technologies. In response to the global COVID-19 emergency, the Ertl lab quickly applied some of these technologies to the development of a vaccine. She illustrates her approach and its advantages below.

Despite a record amount of research efforts on the novel coronavirus that is plaguing the globe, there is still a lot we don’t know, especially regarding the immune response that we develop against it. Therefore, in my lab we are taking a multi-pronged approach to maximize our chances of success.

The coronavirus is known for its unique crown-like shape, given by the “spikes” that cover the outside of the virus. These spikes act like “keys” that insert themselves into a “lock”, known as a receptor on the host cell, which then opens the door to host cell infection. Many researchers have chosen the spike as their vaccine target to prevent COVID-19 because antibodies that can block this key from accessing its lock should protect the host cells from infection. However, studies on other coronaviruses have shown that antibodies may not provide long-term and durable protection, so my lab is taking a dual-pronged approach to mobilize defenders within the immune system.

We have designed a vaccine strategy that targets both the spike and another protein on the viral coat using a proprietary platform developed in our lab to enhance immune response to the vaccine, which has shown promising effects in several settings.

To be more specific, we genetically modify adenoviruses to act as vaccine delivery vehicles because of their ability to stimulate potent and durable immune responses. Adenoviruses, which naturally cause mild or non-symptomatic respiratory illnesses, can be made incapable of replicating and causing infection and used as a platform for vaccine development.

This technology is very effective, relatively inexpensive and safe. Although no human vaccines based on replication-defective adenovirus vectors are currently on the market, several have been extensively tested in clinical trials.

One consideration that needs to be accounted for when working with human adenoviruses is that they are very prevalent in the population and most people are naturally exposed to them in early childhood, so that most adults carry in their blood antibodies that can inactivate adenovirus-based vaccines and reduce their efficacy.

To circumvent the issue of pre-existing immunity, my lab has pioneered the use of a weakened version of an adenovirus that causes infections in animals and has been modified so that it can’t grow in humans. We have used this approach for rabies and HIV vaccines that have shown efficacy in preclinical models.

We are quickly adapting this platform for COVID-19 vaccine development. Another group that I have collaborated with for many years at the University of Oxford is developing an adenovirus-based vaccine that has entered clinical trial stage a few weeks ago, but our approach provides further advantages because, as explained above, it targets two viral proteins and has the ability to further boost the immune response.

I am hopeful that our strategy can be successful because I believe that, at the moment, adenovirus-based vaccines are one of our best shots.

Dr. Ertl’s COVID-19 vaccine research has received critical support from the The G. Harold and Leila Y. Mathers Charitable Foundation, thanks to which she is able to bring her deep knowledge and expertise to the vaccine race to curb the pandemic. Dr. Ertl and Wistar are very grateful to Mathers for stepping in and providing much needed funding to move this research forward as fast as possible and for its continuous support of Wistar science. Dr. Ertl is also the co-founder of Virion Therapeutics, LLC, a Philadelphia-based start-up spun out of The Wistar Institute, developing new vaccine platform technologies.

#Funding4Cure 2020: Supporting Cancer Research Virtually During the Pandemic

Written by The Wistar Institute on . Posted in Featured News.

The Pennsylvania Cancer Alliance, a coalition of the state’s leading cancer research institutions, meets every year in early May for a lobbying initiative to engage legislators and spotlight the impact the Commonwealth Universal Research Enhancement (CURE) Program has on cancer research taking place across the Commonwealth. CURE funding was established in 1998 with money the state received from the Tobacco Master Settlement Agreement.

This year’s face-to-face with cancer research leaders, lobbyists and legislators was canceled due to COVID-19, but the pandemic did not stop advocacy efforts, which were translated into Virtual CURE Lobby Day. Representatives of the member institutions met with lawmakers virtually, over the phone or video, to talk about the need for cancer research funding.

In addition, the Cancer Alliance is raising awareness about the CURE Program through a social media campaign to inform the public about the impact of cancer research on public health.

The urgency of curbing the ongoing pandemic has shifted a large chunk of the global research effort towards finding therapies and vaccines against COVID-19. Even though we are not hearing a lot about it, around the world cancer researchers continue pushing forward their diligent work to tackle a slower and more silent epidemic — cancer, which still causes millions of deaths worldwide every year.

The CURE Program supports broad-based health research to improve the health of all Pennsylvanians and works to support the allocation of a portion of the proceeds of the Tobacco Master Settlement Agreement to cancer research, signed between various tobacco companies and states more than two decades ago.

At Wistar, CURE funding has contributed to the advancement of a non-invasive lung cancer test and new small molecules inhibitors for cancer treatment. It has also supported research by junior investigators to elucidate novel mechanisms underlying tumor initiation and therapy resistance.

The Wistar Institute Appoints Bin Tian, Ph.D., as Professor in the Cancer Center and Co-director of the Center for Systems & Computational Biology

Written by The Wistar Institute on . Posted in Press Releases.

PHILADELPHIA — (May, 1, 2020) — The Wistar Institute, an international biomedical research leader in cancer, immunology and infectious diseases, announces the appointment of molecular systems biologist Bin Tian, Ph.D., as professor in the Cancer Center.

“I am excited to join the high-caliber faculty and collaborative culture at Wistar, a premier research institution with a long, distinguished history of fundamental achievements,” said Tian. “The wide spectrum of technology support at the Institute will be instrumental to advance my work. I look forward to further expanding my research into cancer and immunity through collaboration with Wistar colleagues.”

A molecular biologist by training, Tian focuses on RNA biology and understanding how gene expression is regulated at the post-transcriptional level. His research involves interdisciplinary approaches, including molecular biology, genomics and computational biology, to study RNA biogenesis and metabolism. His lab was among the first to characterize the functional genomics of alternative polyadenylation and has uncovered its role in many diverse cellular processes.

“Bin’s research has led to groundbreaking advances understanding the role of alternative polyadenylation in development and cell differentiation as well as in the context of cancer and cellular stress,” said Dario C. Altieri, M.D., Wistar president and CEO, director of the Cancer Center, and the Robert and Penny Fox Distinguished Professor. “Bin’s work strengthens our RNA biology research and brings expertise in complex computational and genomic methods that will synergize with the work of our scientists across our research programs.”

Tian joins Wistar from Rutgers New Jersey Medical School where he was a professor. Tian serves on several editorial boards and review panels, and has published more than 150 research articles, reviews, and book chapters. In 2000, he received a Ph.D. degree in molecular biology from Rutgers Biomedical and Health Sciences (formerly UMDNJ). After receiving his Ph.D., Tian was appointed a postdoctoral fellow in bioinformatics and genomics at Johnson & Johnson Pharmaceutical Research & Development in La Jolla, CA. Then in 2003, he established his research group at Rutgers New Jersey Medical School where he became a tenured professor in 2014.

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The Wistar Institute is an international leader in biomedical research with special expertise in cancer, immunology, infectious diseases and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. wistar.org.

The Wistar Institute and Batavia Biosciences Launch Collaboration to Manufacture and Distribute Wistar’s Rubella Vaccine Globally

Written by The Wistar Institute on . Posted in Press Releases.

PHILADELPHIA — (April 29, 2020) — The Wistar Institute and Batavia Biosciences announce the launch of a strategic collaboration aimed to streamline the clinical grade manufacture and global distribution of Wistar’s rubella vaccine seed stock commonly known as RA 27/3. In December 2019, Wistar was awarded a $1M grant from the Bill & Melinda Gates Foundation to support this global access-focused international collaboration.

“We must continually find creative ways for non-profit and for-profit companies to work together to make life-saving technologies easily accessible to people around the globe,” said Heather Steinman, Ph.D., MBA, Wistar’s vice president for business development and executive director of technology transfer. “The generous funding support from the Gates Foundation is the glue that has enabled Wistar and Batavia Biosciences to unite with a single mission of ensuring long term supplies of RA 27/3”.

“Combining the established know-how and experience at The Wistar Institute with our technology to manufacture vaccines at low cost and the support of the Bill & Melinda Gates Foundation provides us with an exciting opportunity to increase the distribution of a critical vaccine”, said Chris Yallop, Ph.D., Batavia’s CSO and COO.

Rubella is a contagious viral disease that mainly affects children and young adults, typically manifested with mild clinical symptoms. However, rubella infection during pregnancy, especially during the first trimester, can result in severe complications including miscarriage, fetal death, stillbirth, and congenital malformations, known altogether as congenital rubella syndrome (CRS).

The rubella vaccine was developed at Wistar in 1969 in the laboratory of Stanley A. Plotkin, M.D. The vaccine is safe and effective at providing long-lasting protection. The number of countries using rubella vaccines in their national immunization programs is steadily increasing, and global rubella vaccine coverage in 2018 was estimated at 69% by the World Health Organization. Despite this progress, rubella control is lagging behind, and several countries have neither introduced the vaccine nor set elimination or control targets.

One major issue is supply shortage, mainly due to insufficient production capability. The number of companies that produce rubella vaccines has been steadily decreasing, causing global shortages of the vaccine.

Batavia shares with Wistar a focus on rapidly accelerating the development of vaccines and other biopharmaceutical product candidates from discovery to market to improve global health. This collaboration with the Netherlands-based company bolsters the developing relationship between geographies as Wistar also recently announced the establishment of the Wistar-Schoemaker International Postdoctoral Fellowship with the Leiden University Medical Center in the Netherlands (LUMC), which will bring recent Ph.D. graduates trained at LUMC to Wistar to advance their research education under the mentorship of cutting-edge biomedical research leaders.

Thanks to support from the Bill & Melinda Gates Foundation, Wistar will be able to archive the existing supplies of research-grade rubella virus seed stock and transfer the necessary supplies to Batavia, to enable the development of readily accessible good manufacturing practice (GMP)-grade rubella drug substances and drug product formulations, with the intent to distribute these critical materials to vaccine manufacturers around the world through a universal license agreement construct.

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The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. Wistar’s Business Development team is dedicated to advancing Wistar Science and Technology Development through creative collaborations. wistar.org.

Batavia Biosciences significantly contributes to ease human suffering from infectious diseases and cancer by improving the success rate in the translation of candidate medicines from discovery to the clinic. We offer our innovative technologies and in-depth know-how in order to help our partners to complete preclinical phases in biopharmaceutical product development at higher speed, reduced costs and increased success. The company focuses on the early stages of product development including cell line generation, upstream process development, purification development, product characterization and clinical manufacturing. Headquartered in Leiden, the Netherlands, with a subsidiary in Woburn, Massachusetts, and offices in Hong Kong, Batavia Biosciences is privileged to have strong strategic partners worldwide. For more information visit www.bataviabiosciences.com.

Uncertain Times: Wistar’s Historic Strides in the Time of COVID-19

Written by The Wistar Institute on . Posted in Featured News.

This is week six of the stay-at-home order in Pennsylvania and Darien Sutton, associate director of Communications & Marketing, caught up again with President and CEO Dario C. Altieri, M.D., for their second virtual chat about what’s going on with the COVID-19 emergency.

Sutton: What’s up with the buzz cut?

Altieri: This? Oh, this is my homemade pandemic cut. According to the Pennsylvania Department of Health, we will need fewer than 50 new COVID-19 cases per 100,000 people to reopen things in Philadelphia. And not just for one day, but for two weeks straight. Currently, we are at about 400, a long way away. So, I figured it will be a while before any barber shop reopens and I took matters into my own hands. Literally. Plus, the look reminds me of the good old days in the 27th Artillery Regiment.

Sutton: Speaking of the pandemic instead of your looks, what are we seeing right now?

Altieri: The numbers continue to be worrisome. Unfortunately, the U.S. is the world epicenter of the COVID-19 pandemic with over 900,000 confirmed cases and more than 54,000 deaths. About half of those numbers are in two states, New York and New Jersey. We have heard a million times about flattening the curve. The curve has flattened but the cases have not yet come down. Right now, it seems more like a plateau, not dissimilar from what European countries have experienced.

Sutton: And yet, we hear talks about reopening the country, restarting the economy and going back to some sort of normalcy. Are we ready to do that?

Altieri: Clearly, one size doesn’t fit all: Certain parts of the country have seen relatively few cases. Others have done very well at containing the outbreak. Others yet may not have even peaked. There are still a lot of things that we don’t know about the virus and how it spreads. I think we should be very, very cautious at what we do next and how we do it. If you had told me two months ago how devastating COVID-19 would be, I would not have believed it. I am stunned that as a society we seem to tolerate an average of 2,000 COVID-19 deaths a day.

Sutton: And talking about the unknowns, what are the most important things that we should figure out before we reopen?

Altieri: First, we still don’t know what the impact of asymptomatic spreading is. This is the scenario of someone next to you on a commuter train or in line at a grocery store, who is not sneezing, coughing or anything and yet is spreading the virus. Earlier data from Wuhan suggested that this kind of spreading is rare, maybe around 1%. But more recent studies suggest that the number is actually much, much bigger, maybe even in the high 30%. And, second, how protective are the antibodies against COVID-19 that we find in people after an infection? A study from New York suggests that more than 15% of people who never complained of COVID-19 symptoms actually have antibodies against it. This says that the virus has been with us for much longer than we thought. But does it also mean that those people are protected against (re)infection?

Sutton: Moving on to Wistar now, did anything happen since the last time we spoke?

Altieri: Oh, not much. We simply made history. Again. David Weiner’s recombinant DNA vaccine against COVID-19 entered clinical trials this month. This is only the second vaccine against COVID-19 that is being tested in the U.S. Accrual has been brisk, and the study is apparently on track to successfully complete enrollment of about forty healthy volunteers by the end of April.

Sutton: Why is that making history?

Altieri: Well, David and his collaborators at Inovio moved the COVID-19 vaccine from design to FDA-approved clinical testing in 83 days. This is breakneck speed, I think unprecedented for drug discovery and development. Second, David has accumulated impressive preclinical results suggesting that his vaccine generates a robust immune response in laboratory animals. Of course, we need to see what happens in humans, but the initial data suggest that the vaccine will awaken our immune system against COVID-19. Phase 2 efficacy trials will tell whether this translates in protection against the virus.

Sutton: This is clinical development 101. Since Wistar doesn’t have a hospital, how can Wistar support the advancement of the vaccine?

Altieri: We have a world-class infrastructure of people and facilities at Wistar that will be instrumental to advance this vaccine candidate through the process. We have also received an incredible outpouring of support and generosity from so many people to finance these and other research efforts focused on COVID-19. This has allowed us to move really fast and in multiple research directions creating amazing new collaborations, which is typical of how Wistar approaches science.

Sutton: Certainly, strong reasons to be upbeat in face of the current bleakness. Any other reason to look up?

Altieri: Absolutely. Gronk reunited with TB12 in Tampa. Watch out NFC South.

Spotlight on Wistar COVID-19 Researchers: Luis Montaner, D.V.M., D.Phil., & Joseph Salvino, Ph.D.

Written by The Wistar Institute on . Posted in Featured News.

Dr. Luis Montaner is an HIV expert focused on finding new ways to boost the natural function of the immune system to combat infection or viral-associated disease. Dr. Joseph Salvino is a medicinal chemist and an expert in drug discovery and identification of novel small molecule lead compounds. The two have combined their expertise to design a strategy to modulate the immune response to viral infections using novel small molecules. They discuss the basis of this approach and how they are advancing it.

Montaner: We are born programmed to resist viral infections. One of the key weapons our immune system uses to respond to viruses is interferon, which “interferes” with the viral replication. However, sometimes our system is not effective. Our goal is to amp up the natural immune response to COVID-19 in a targeted way without inducing greater inflammatory damage in the lung.

Salvino: Interferons activate the immune response by engaging a specific receptor present on the cell surface. We are developing compounds that stimulate binding of interferons to their receptor and activate signaling to the cell to initiate an antiviral response. We have some interesting lead compounds that we are testing to confirm they have the intended biological effect without toxicity.

Montaner: Joe and I have been collaborating for the past three years to find small molecules that can modulate immunity in HIV by acting on the interferon response, as one of my lab’s interests is what happens when this response becomes chronic and poses problems.

Salvino: For this project, we have now tested about 20-30 thousand compounds based on computer models and predictions. We were looking for inhibitory compounds that block the interaction of interferons with their receptor, but we have also come across stimulatory compounds that have the opposite effect and can actually serve as a glue between ligand and receptor.

Montaner: When the COVID-19 outbreak started, we realized we had those molecules in our hands that could potentially be helpful and limit the disease by amplifying the interferon antiviral response. These small molecules act as cement between interferon and receptor, making the interaction more stable and, as a consequence, strengthening the stimulation provided on the immune cell. We don’t want to make it irreversible, though. We want to maintain an off switch because the immune cells are not programmed to be on a constant inflammatory state and that could lead to tissue damage, for example to the lungs in the case of COVID-19.

So, we looked back at several molecules that in our studies made the interferon response better. The platform we developed to test our inhibitory compounds in vitro and in vivo gives us the advantage of time because we don’t need to set up new systems and assays; we already have them in place. Basically, we are steps ahead in the process because we already have candidate molecules and the appropriate tools to test them. We are evaluating these compounds to track their effect on the immune response in vivo.

Salvino: There are limited small molecule drugs available to fight viral infections and, in general, they work by directly interacting with the virus. For example, a compound could bind to the “Spike” of COVID-19 to block the virus from entering the host cells; or it could directly bind to an essential component in the virus to reduce its ability to function. However, viruses have the ability to mutate and become resistant to drugs, and that small molecule could lose effectiveness. Our approach is different because it targets the host and has a reduced likelihood of causing resistance compared to virus-directed approaches.

Montaner: These small molecule drugs can potentially amplify the natural antiviral response and prevent the COVID-19 virus from establishing an infection, or rapidly fight it off. In theory, such therapeutic booster could be used alone at onset of symptoms or later on in combination with other antiviral drugs.

Salvino: This work is very collaborative. Our labs complement each other, since my expertise in organic and synthetic chemistry is combined with Luis’s immunology and biology expertise.

Montaner: As a basic biomedical research institute, Wistar makes fundamental discoveries and generates proofs of concepts for potential new therapies. For example, after identifying new compounds, we study their activity and test them in preclinical models. Once these steps are complete, partnerships with industry become critical in order to translate our discoveries into new medicines.

We believe our work to identify small molecules to boost the immune response against viral infection could potentially be important in the COVID-19 crisis, and for other diseases, but even getting to the point at which a new candidate drug is attractive to industry partners requires extensive work and robust financial support.

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Spotlight on Wistar COVID-19 Researcher: Daniel Kulp, Ph.D., Associate Professor 

Written by The Wistar Institute on . Posted in Featured News.

Principal investigator Dr. Daniel Kulp is one of a group of Wistar scientists undertaking coronavirus research in response to the pandemic. A protein engineering expert, his lab focuses on rational vaccine and therapeutic antibody design for a variety of priority infectious diseases. Here he explains his interesting approach and its advantages.

The immune system is highly complex and encompasses a vast amount of cell types and compartments within the human body, therefore it can be stimulated into action in many ways. Though there is no silver bullet when it comes to vaccines, researchers have explored multiple approaches to achieve protective immunity.

Most traditional vaccines are empirically designed, meaning that a whole attenuated or killed virus is used to prompt the immune response. Thanks to a deeper knowledge of the pathogen and its mechanisms, more recent, rational approaches can be utilized to engineer specific virus-derived molecules that elicit stronger, predictable and more focused immune responses and are safer and not infectious.

In my lab, we take a bottom-up engineering approach and build precise structures into our vaccines, using computer simulations to design vaccines that help steer the immune system toward protective responses against specific pathogens. This rational approach enables us to generate improved vaccines by hypothesizing and iterating new concepts.

We specialize in designing nanovaccines, which consist of extremely small (‘nano’) particles that are similar in size and shape to bacteria and viruses and are used to display multiple copies of an antigen. Such multi-valent displays within a single vaccine can significantly enhance induced immunity.

It sounds like science fiction, but it’s not a completely new concept — in fact, the first licensed nanoparticle vaccine was against hepatitis B in 1981. The early nanoparticle vaccines were limited to nanoparticles that could be found in viruses. However, we have entered into a new era where technologies built in my lab and others have enabled us to engineer synthetic nanoparticle vaccines for a variety of infectious targets. Our unique vaccine design approach in collaboration with researchers at The Scripps Research Institute has led to the development of an HIV vaccine that has entered phase 1 clinical trials.

One of the advantages of this approach is that it is amenable to rapid delivery technologies that increases the speed at which a vaccine candidate can be advanced. So, when the new coronavirus emerged, we got to work to apply this technology and our expertise to fight SARS-CoV-2 (the virus responsible for COVID-19 disease).

A critical step in developing nanovaccines is the selection and design of the antigen to display on the nanoparticles. We choose regions of the virus called epitopes, which are crucial for the virus to function, in order to stimulate a response that can block the virus from infecting our cells.

For coronaviruses to enter host cells, fusion of the virus with the cell membrane must take place. This process is regulated by a specific part of the viral Spike protein, which adorns the surface of coronaviruses. We have engineered a nanoparticle vaccine that targets this epitope and creates robust antibody responses in mice. The lab is now ready to begin testing the vaccine in large animals before translating into the clinic.

SARS-CoV-2 possesses a receptor (like many viruses) that is another vulnerable target for protective antibodies. We have demonstrated that certain regions of the receptor for influenza and HIV could be engineered onto various self-assembling nanoparticle scaffolds. We are starting to translate these concepts to SARS-CoV-2. In addition to nanoparticle vaccines, we are beginning to engineer “decoy receptors” to trick the virus and prevent infection. The big picture is that these soluble decoys can be given to patients after they get infected to boost immune defenses and help them recover with only mild symptoms. The decoy therapies will be of critical importance to give people around the world the confidence to return from quarantine.

These approaches have big potential but can require significant monetary resources to put a vaccine or therapy through preclinical testing and the clinic, so the more support we have the faster we will be able to advance our work and potentially protect billions of vulnerable individuals worldwide.

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Dr. Rugang Zhang Named Leader of the Immunology, Microenvironment & Metastasis Program of The Wistar Institute Cancer Center

Written by The Wistar Institute on . Posted in Featured News.

The Immunology, Microenvironment and Metastasis (IMM) Program explores the basic mechanisms of host-tumor interactions, immune responses and metastatic dissemination to create novel translational avenues for cancer diagnosis and therapy such as immunotherapy.

Wistar professor Rugang Zhang, Ph.D., has recently been appointed leader of the IMM Program, transitioning from his previous appointment as a co-leader of the Gene Expression & Regulation Program (GER). He succeeds Dmitry Gabrilovich, M.D., Ph.D.

Dr. Zhang leads a very productive lab studying the biology of ovarian cancer, the most lethal gynecological malignancy in the developed world, with the goal of developing novel therapeutic approaches to combat the disease with precision. In particular, the lab focuses on alterations in epigenetics, the set of heritable mechanisms that define how our genetic information is read and executed.

In the following Q&A, Dr. Zhang explains the impact and reflections his new appointment will have on the IMM Program and his own research.

Q: You have been part of the GER program ever since you joined Wistar in 2012. Does your new role and affiliation reflect a change in research direction for your lab?

A: In the current era, biomedical research moves at a breathtaking pace and the lines among different disciplines blur quicker than ever before. In the past few years, my research has expanded into understanding the interplay between ovarian tumor and its host microenvironment, in particular the immune microenvironment. While affiliated with the GER Program, I have been routinely attending the IMM programmatic meetings and have collaborated quite extensively with members of the Program prior to this change of affiliation. So in short, yes, the change is, to a large degree, a reflection of the natural evolution of my own research program.

Q: What are the immunology, microenvironment and metastasis aspects of ovarian cancer you are exploring?

A: We are actively studying the effects of an emerging class of therapies that work by targeting epigenetic pathways that are critical in ovarian cancer. Interestingly, in addition to acting on cancer cells, epigenetic drugs have a profound effect on the tumor microenvironment, including immune cells and other cells that facilitate cancer progression. We published a number of papers demonstrating that epigenetic drugs can work together with immunotherapy, such as immune checkpoint blockade, to suppress ovarian cancer. This approach may also be beneficial to prevent the development of resistance to individual therapies. In addition, we are very interested in exploring how epigenetic regulators control the dissemination of ovarian cancer, especially in the abdominal cavity. This process is comparable to metastasis in other types of solid tumors. In essence, we are studying immunology, microenvironment and metastasis from a gene expression and epigenetics point of view.

Q: What will your expertise and scientific accomplishments bring to the IMM Program?

A: As discussed above, my lab brings to the program a mechanistic perspective to study tumor microenvironment and metastasis. In addition, I believe our previous accomplishments in dissecting the interaction between ovarian cancer and the associated microenvironment will add new expertise to the Program and create opportunities for new synergy and collaboration.

Q: What is your vision for the Program moving forward in terms of research priorities and focus? How do you plan to implement it?

A: I envision the Program as a catalyzer of mechanism-guided translational research, complementing and synergizing with the other two Programs in our Cancer Center. I believe a stronger focus on mechanisms would enhance the vast therapeutic potential of the research conducted in the Program. We would like to foster disease-focused, collaborative research opportunities centered around the immune microenvironment and immunotherapy and leverage the unique strength in vaccine development in the IMM Program for cancer applications. Another short-term priority is taking advantage of the enormous amount of publicly available research databases to create a centralized database that could be used to generate clinical evidence-based hypothesis. The focuses of the IMM Program will be refined and sharpened through programmatic efforts and upcoming recruitment activities.

Q: What collaboration opportunities do you see?

A: In the present-day cancer research setting, collaboration is not an option, it’s a necessity, because development of effective therapies demands a more holistic view of cancer that looks at malignant cells in their ecosystem. Essentially, we are studying cancer as a disease organ whose uncontrolled growth depends on both cancer cells and their supporting microenvironment. For this reason, I see many many intra- and inter-programmatic collaboration opportunities. Specifically, my own research program will interface with pretty much everyone in the IMM Program. For example, we are actively collaborating with Dr. Mohamed Abdel-Mohsen on characterizing the role of sugar molecules in ovarian cancer dissemination and metastasis and with Dr. Andrew Hu on exploring the cellular stress response as a vulnerable target in defined subgroups of ovarian cancer. Of course, my research has and will always be rooted in the basic mechanisms of gene expression, which is the reason why I was in the GER Program for the past eight years. In addition, the Molecular & Cellular Oncogenesis Program (MCO) is critical in our understanding of cancer at the system biology level, which is also integral to my research program. In conclusion, I think my move to the IMM Program will strengthen both collaboration within the Cancer Center and across the Institute.

Moving the Needle Forward: Wistar Research Leads to a Coronavirus Vaccine Entering Human Trials and Additional Wistar Coronavirus Research Projects Underway

Written by The Wistar Institute on . Posted in Featured News.

While the world struggles with a growing number of people sickened with COVID-19 and health care workers engage in a tireless and heroic mission to save lives, biomedical researchers are on the front lines of a parallel and equally critical battle to develop new tools to effectively diagnose, treat and prevent a disease we are still learning about.

Scientists at The Wistar Institute’s Vaccine & Immunotherapy Center (VIC) have been working long hours and over weekends, devising new strategies to apply their expertise and technological platforms to combat SARS-Cov-2. 

So far, the work has paid off. The second COVID-19 vaccine to move into clinical testing in the U.S. is due in part to Wistar’s effort and comes from the team led by Dr. David Weiner and including Drs. Daniel Kulp, Ami Patel and Kar Muthumani, in collaboration with biotech company Inovio Pharmaceuticals, Inc.

This vaccine, based on synthetic DNA technology, was advanced in record time from computer design to preclinical testing in just under three months. Results from preclinical studies show the vaccine is effective at inducing both antibody and T cell-mediated responses soon after delivery in mice and guinea pigs, allowing researchers to unlock the next step — human testing subsequent to FDA approval.

Data from these studies are available to the scientific community while the manuscript is under consideration for publication in a high-impact journal.

Even though the vaccine will go through further testing in the lab as new tools and reagents become available, scientists have passed the baton to their pharmaceutical partner and the doctors and clinical experts working with the company to evaluate the safety of the coronavirus vaccine in people.

Announced by Inovio on Monday, April 6, the vaccine just entered a phase 1 clinical study coordinated by the University of Pennsylvania. 40 healthy adult participants in Philadelphia and Kansas City, Missouri will receive two vaccine doses four weeks apart, and initial data on immune responses and safety from this study are expected by late summer.

“I am extremely proud of all the work done by our scientists for this vaccine and the role played by Wistar as an academic engine of new technologies that are the basis for future medicines,” said Dario C. Altieri, M.D., Wistar president and CEO. “Hopefully, one day not so long from now, we will have a preventative vaccine to help curb the pandemic. It would be another enormous Wistar contribution to human health.”

In these times we need as many tools as possible to stem the pandemic. Wistar scientists are actively developing other vaccine approaches and therapeutic strategies, ranging from tricking the virus into attaching to decoy receptors to prevent it from infecting cells, to reducing inflammation that causes disease severity in those infected with the virus, to alternative ways to make and deliver protective antibodies that will neutralize the virus.

Although in early stages, most of this research has the potential to be advanced fairly quickly due to the nature of the approaches and our scientists’ previous experience with tackling other infectious agents.

“We are very excited about the potential of our COVID-19 vaccine,” said Weiner. “The preclinical results thus far motivate us to focus our efforts in additional directions and do our best to advance more approaches that can ultimately make a difference in this pandemic.”

To catalyze Wistar’s coronavirus research endeavor, the Institute recently launched the Wistar Coronavirus Discovery Fund, which will support a range of research programs and enhance the ability of our scientists to pursue innovative solutions as quickly as possible.

As the World Health Organization remarked, “Coronavirus research has accelerated at incredible speed…” because scientists, funders and international organizations have come together to solve the crisis. 

“We are all in this together and together we can all do our part,” said Weiner.