The Wistar Institute: A Leader in Biomedical Research

• We are co-creators of a rotavirus vaccine that contributes to saving U.S. children from 250,000 emergency room visits and 70,000 hospitalizations each year.
  
  
• The world’s first rabies vaccine was invented at Wistar. Today, our rabies vaccines are used worldwide to prevent rabies-related deaths in humans and wildlife.
  
  
• Thanks to our rubella vaccine, which is given as part of the routine MMR immunization, rubella infection (German measles) was declared eliminated in the U.S. in 2004.
  
  
• We developed vaccines and cell culture technologies critical for the development of other vaccines in use today throughout the world.
  
  
• We discovered that cell populations have a limited lifespan, defining the concept of aging at the cellular level and laying the foundations for the study of the role of aging in cancer pathology.
  
  
• We pioneered the monoclonal antibody technology – the original immunotherapy used to diagnose and treat cancer and autoimmune diseases.
  
  
• We identified genetic alterations linked to the development of blood cancer, paving the way for the development of molecular therapies.
  
  
• Our Wistar rat is one of the first standardized laboratory models critical for advancing biomedical science. Our cell models are used around the globe to test new medicines.

• We are developing novel, DNA-based technologies as immunotherapies for emerging infectious diseases and cancer.
  
  
• We are helping advance the first Zika vaccine successfully tested in clinical trials.
  
  
• We are running the first, largest HIV cure trial to boost patients’ immune systems and eradicate the virus, and we are exploring new avenues to defeat HIV viral latency.
  
  
• We are generating novel treatments to combat antibiotic-resistant infections.
  
  
• We are studying the role of the immune system and the tumor microenvironment in tumor progression and response to therapy.
  
  
• We are applying DNA-based vaccines and monoclonal antibodies to cancer immunotherapy and finding new immunotherapy drug combinations.
  
  
• We are developing the first drugs for cancers caused by viral infections, including Epstein-Barr virus and HPV.
  
  
• Our melanoma research lab – one of America’s largest outside the National Institutes of Health – is studying how genes, age and other factors impact melanoma progression.
  
  
• We are developing novel small molecules as targeted therapeutics for melanoma and prostate, brain, nasopharyngeal, and blood cancer.
  
  
• We are advancing noninvasive blood tests for lung and ovarian cancer.
  
  
• We are pursuing a novel diagnostic platform for glioblastoma, a common, fatal form of brain cancer.

Brain

• Louise Showe, Ph.D., has devised a novel molecular test that is currently under development by a Wistar spin-out company, ISOMA Diagnostics, LLC, into a biomarker to classify patients with glioblastoma, the most common and the deadliest type of primary malignant brain cancer in adults. Classification of patients into appropriate sub-types has the potential to guide targeted treatments and become a powerful resource in clinical trials.

Breast

• Breast cancer research in progress at Wistar aims to better understand how breast cancer spreads and metastasizes, with goal of identifying treatment opportunities. There are three key areas of focus:
  
  
  • Disruption in regulation of gene expression involved in breast cancer initiation and progression;
    
    
  • Molecular mechanisms of metastasis to the brain and interaction between brain cells and metastatic breast cancer cells;
    
    
  • Characterization of naturally occurring variants in the p53 gene and how they affect genetic predisposition to breast cancer in different populations.

Cervical

• Cervical cancer is the fourth most common type of cancer for women worldwide and has been linked to human papillomavirus (HPV) infection. Using a novel synthetic DNA-based technology, David Weiner, Ph.D., in collaboration with Inovio Pharmaceuticals, Inc., has created a therapeutic vaccine that targets HPV and causes tumor regression. Another innovative vaccine technology developed by Hildegund C.J. Ertl, M.D., is being pursued by the Wistar spinout Virion Therapeutics, LLC, to create new immunotherapeutic strategies for HPV-associated cancers.

Lung

• Lung cancer remains the primary cause of cancer-related deaths worldwide. Because early detection protocols are inadequate, disease symptoms do not appear until the cancer is advanced. The development of alternative non-invasive tools to assess difficult-to-diagnose nodules is a critical goal in pulmonary medicine. Our scientists have developed a novel non-invasive platform for the diagnosis of lung nodules in non-small cell lung cancer patients based on gene expression from whole blood. This highly accurate technology, created by Louise Showe, Ph.D., has been licensed to OncoCyte Corporation and is currently in clinical trials and development.

Melanoma

• Melanoma research has been a hallmark of cancer research at Wistar for decades. The Wistar Melanoma Research Center is one of the largest melanoma research programs in the U.S. and has contributed important advancements in the understanding of the relevant molecular pathways, the role of stem cells in melanoma, and the creation of research tools and models that serve the global melanoma research community. Currently, Wistar scientists Meenhard Herlyn, D.V.M., D.Sc. and Jessie Villanueva, Ph.D., are investigating the mechanisms of therapy resistance and studying how the tumor microenvironment affects melanoma progression.

Ovarian

• Ovarian cancer is the most lethal gynecological malignancy in the developed world. Research at Wistar aims at developing novel therapeutic approaches to combat the disease with precision, leveraging new mechanistic insights into how alterations in epigenetics (heritable changes that affect gene expression without alterations in the underlying DNA sequence) contribute to ovarian cancer. Wistar has also created a novel cell-based therapeutic approach in which T cells are engineered in the laboratory so that they will specifically target ovarian cancer. This approach, based on the chimeric antigen receptor T-cell (CAR-T) technology, has been licensed for further clinical development to ITUS Corporation.

Prostate

• Dario Altieri, M.D., has identified a novel molecular pathway that supports prostate cancer progression and has created a novel small molecule inhibitor called gamitrinib for advanced prostate cancer. This inhibitor specifically targets the mitochondria, the energy production centers in the cells, and is effective at inhibiting localized and metastatic prostate cancer growth in preclinical models. Gamitrinib is about to enter clinical trials.

Chikungunya

• The Chikungunya virus (CHIKV) is transmitted through mosquitoes and causes fever and joint pain that can sometimes become severe and disabling. Outbreaks of the virus have occurred in Africa, Asia, and Europe, and in late 2013, the virus was first seen in the Americas. No vaccine to prevent or treat this virus currently exists. David Weiner, Ph.D., and Kar Muthumani, Ph.D., have developed a combined synthetic DNA-based approach with DNA-encoded monoclonal antibodies and a synthetic DNA vaccine that has been shown to produce rapid and sustained protection against the virus in preclinical models.

Epstein–Barr virus (EBV)

• Epstein-Barr virus (EBV) latent infection is associated with several human malignancies, including Burkitt’s lymphoma, nasopharyngeal carcinoma and Hodgkin’s disease. Wistar scientists have characterized several biochemical pathways that control the stability, replication, and gene expression patterns of the latent virus. Paul Lieberman, Ph.D., has developed a small molecule inhibitor of the EBV protein EBNA1 for EBV-associated malignancies. Preclinical development of this compound was largely supported by Wellcome, a biomedical research charity based in the United Kingdom. The compound has been licensed for clinical development and commercialization to Cullinan Oncology, LLC.

Ebola

• Ebola virus infection causes a severe hemorrhagic fever with a 50% fatality rate. David Weiner, Ph.D., has designed synthetic DNA vaccine candidates and DNA-encoded monoclonal antibodies targeting Ebola virus. Both approaches demonstrated efficacy and durability of the immune responses in animal models.

HIV/AIDS

• The HIV-1 research program at Wistar, led by Luis Montaner, D.V.M., D.Phil., is studying the mechanisms of immunodeficiency caused by HIV infection, investigating novel ways to boost the immune system function against the virus, and exploring new avenues to conquer and defeat viral latency, one of the most challenging obstacles to achieving a cure for HIV. The Montaner Lab is co-leading a consortium of more than 30 of the nation’s top HIV investigators called the Delaney BEAT-HIV Collaboratory. In 2016 the Consortium received a nearly $23 million grant from the National Institutes of Health for HIV cure research, to test combinations of novel immunotherapies in clinical trials.
  
  
  • One study is based on combination of a special type of interferon to strengthen the immune system and antibodies that can neutralize HIV.
    
    
  • In another study, researchers will genetically modify CD4+ T cells purified from study participants to make these cells highly specific in recognizing HIV-infected cells. This strategy will be combined with additional gene therapy approaches to make these T cells resistant to HIV infection.

Influenza (Flu)

• Currently available vaccines for the prevention of seasonal influenza (flu) virus infection have limited ability to induce immunity against diverse circulating strains. David Weiner, Ph.D., has engineered a synthetic DNA vaccine shown to produce broad immune responses against these H3N2 viruses, an influenza A subtype that has led to high morbidity and mortality in recent years. The novel Wistar vaccine has the potential to protect against multiple strains of influenza, offering better immunity against the seasonal illness.

Lassa

• Lassa fever is a deadly disease endemic to West Africa associated with annual outbreaks. The Weiner Lab is working on creating a synthetic DNA vaccine and advancing it to clinical trials with support from the Coalition for Epidemic Preparedness Innovations (CEPI).

Malaria

• Malaria is a leading cause of death in infants and children in sub-Saharan Africa and other developing areas of the world. The disease is caused by a parasite that is transmitted through mosquito bite and is able to evade the immune system and enter the bloodstream to eventually migrate to the liver, where it establishes infection. David Weiner, Ph.D., is applying the synthetic DNA vaccine technology to develop a vaccine for Malaria with support from the Bill & Melinda Gates Foundation.

Mayaro

• MAYV infection causes fever, rash, headache, nausea, and vomiting for prolonged periods in many people and can lead to persistent and debilitating muscle and joint pain. There are no approved treatments or preventative medicines for Mayaro fever. Although infection used to be confined to some heavily forested areas of South America, the virus has the potential to spread beyond its historical geographic range, as Zika virus did a few years ago, and become a new global threat. Kar Muthumani, Ph.D., has developed a novel synthetic DNA vaccine targeting MAYV that induces robust and specific immune responses and provides complete protection from disease in preclinical studies.

Middle East Respiratory Syndrome (MERS)

• Middle East Respiratory Syndrome (MERS) is a highly infectious respiratory disease predominant in the Middle East and is defined as a potential public health emergency by the World Health Organization. David Weiner, Ph.D., and collaborators at Inovio Pharmaceuticals, Inc, are leading the charge to rapidly advance a MERS vaccine through phase 2 clinical development, with support from the Coalition for Epidemic Preparedness Innovations (CEPI).

Rabies

• Wistar scientists are credited with the creation of a post-exposure vaccine for people and a vaccine for wildlife. Both are used worldwide and have helped to make rabies-related human death a rarity in the U.S. and many other countries. Hildegund C.J. Ertl, M.D., is now developing a novel preventative rabies vaccine that could provide rapid immunity following a single administration and could benefit populations in high-risk regions.

Zika

• A mosquito-borne infection associated with birth defects and neurological complications in adults, Zika virus gained notoriety by spreading rapidly through Brazil, the Caribbean, and the southern U.S. in 2015-16. No approved vaccine or treatment is currently available. David Weiner, Ph.D., contributed technology critical to the development of the expedited approval by the FDA to be the first Zika vaccine to enter clinical trials — a novel, synthetic DNA vaccine shown to be safe and effective at inducing immune response.