Scientists have discovered a previously unknown enzymatic function of the Epstein-Barr Virus (EBV) protein EBNA1, which could lead to new approaches for treating EBV-associated cancers. The study sheds light on how this protein helps replicate and maintain the viral genome in infected cells.
The EGR1 transcription factor inhibits expression of pro-inflammatory genes in macrophages, blunting their activation and the immune response. This discovery sheds light on the fundamental process of macrophage maturation, which is critical for inflammation.
A new humanized mouse model has revealed that tumor-infiltrating mast cells are connected to immune checkpoint inhibitor resistance in melanoma. Combining anti-PD-1 therapy with small molecule inhibitors able to deplete mast cells caused complete regression of tumors and prolonged survival in mice.
A new humanized mouse model has revealed a central role for mast cells in immune checkpoint inhibitor resistance in melanoma. The study found that depleting mast cells improves treatment responses to anti-PD-1 therapy, suggesting a potential new approach for treating this type of cancer.
Mutations in the ARID1A gene increase glutamine metabolism in ovarian cancer cells, which can be blocked to target ARID1A-mutant tumors. Glutaminase inhibitors like CB-839 show promise as a standalone or combination therapy for clear cell ovarian carcinoma.
Scientists at The Wistar Institute have developed an ACSS2 inhibitor that impairs cancer growth in preclinical models by depriving malignant cells of a critical nutrient source. This approach targets acetate metabolism, which is essential for tumor growth under conditions of low nutrient and oxygen availability.
Wistar scientists have discovered a new class of compounds that combine direct antibiotic killing with a rapid immune response to combat antimicrobial resistance. These dual-acting immuno-antibiotics target an essential bacterial pathway and stimulate the adaptive immune system, showing promise in treating pan drug-resistant infections.
Scientists at The Wistar Institute, INOVIO, AstraZeneca, and Indiana University are developing synthetic DNA-encoded monoclonal antibodies (DMAbs) to combat COVID-19. These novel therapeutics instruct the body to produce highly specific antibodies against pathogens, offering advantages in scale-up and delivery.
Scientists at The Wistar Institute have developed a synthetic DNA vaccine against Powassan virus, which causes a deadly tick-borne disease with neurological consequences. The vaccine elicits broad immune responses in mice and provides protection in a challenge animal model.
Researchers at The Wistar Institute have developed novel anticancer compounds that inhibit the IRE-1/XBP-1 pathway, a key player in ER stress response. These inhibitors show selective activity against malignant B cells, including MM and CLL, with improved tumor specificity.
Researchers at The Wistar Institute discovered that CLL cells downregulate STING protein to allow for increased expression of B cell receptors on their surface, promoting survival. This reduction in STING expression enables stronger B cell receptor signaling, supporting CLL cell survival.
Researchers developed DNA-based nanovaccines that stimulate killer T cell immunity, resulting in tumor control. The synthetic vaccines enhanced CD8 T cell activation and induced muscle cell apoptosis, attracting macrophage infiltration and activating immune responses.
The BEAT-HIV Collaboratory recommends prioritizing viral measurements to accurately measure persistent HIV reservoirs in cure-directed clinical studies. These guidelines aim to standardize measurement approaches and aid researchers in their quest to find a cure for HIV.
Breast cancer cells send pro-tumorigenic messages to normal cells through extracellular vesicles, reprogramming mitochondrial function and promoting migration. This process may provide a novel target for disrupting cancer progression.
Researchers at The Wistar Institute identified a cell-surface glycomic signature associated with persistent HIV transcription in T cells. This signature, characterized by the presence of fucose and Sialyl-LewisX, may help target hidden HIV reservoirs during antiretroviral therapy.
A newly discovered molecular pathway involving topoisomerase 1 (TOP1) enables the detection of DNA in the cytoplasm, triggering inflammation and cellular senescence. This pathway may be targeted to enhance the response of cancer cells to immune checkpoint blockade therapy.
Researchers have discovered a rare African-specific variant of the TP53 gene that causes iron accumulation in macrophages, leading to poorer responses to bacterial infections. However, this variant also improves response to malaria toxin, potentially offering protection against severe inflammation and disease severity.
Researchers have identified a new therapeutic strategy to combat chemotherapy resistance in ovarian cancer by targeting the NAD+ metabolic pathway. Combining cisplatin treatment with pharmacological inhibition of NAMPT suppresses the outgrowth of resistant cancer cells and prolongs survival in a preclinical model.
Scientists at The Wistar Institute have developed a synthetic DNA-based platform to drive in vivo production of broadly neutralizing anti-HIV antibodies. These results show that the platform can produce potent antibodies with strong neutralization ability, comparable to recombinant antibodies. Additionally, combining multiple antibodie...
The American Cancer Society has awarded Dr. Dmitry Gabrilovich a $400,000 research professorship to explore the roles of myeloid immune cells in cancer and develop new approaches to target tumor immunity.
Researchers at Wistar Institute have received a major grant to further research on new melanoma targeted therapies integrating the role of the tumor microenvironment. The team aims to identify novel targets and potential inhibitors to disrupt therapy resistance in older melanoma patients.
Scientists at The Wistar Institute have identified a novel mechanism by which astrocytes promote cancer cell growth and metastasis in the brain. The pro-metastatic effect is mediated through the activation of the PPAR-gamma pathway, providing a new lead for PPAR-gamma antagonists in cancer therapy.
Researchers at The Wistar Institute developed a novel anticancer molecule targeting the MFF-VDAC1 complex to regulate mitochondrial cell death. The compound effectively delivered potent anticancer activity in preclinical models of various cancer types.
Zachary Schug receives $2,679,000 NIH award to study link between high sugar/fat diet, alcohol use and cancer. He aims to uncover molecular mechanisms underlying this connection and develop novel therapies.
The Wistar Institute has been awarded $12M to investigate the impact of opioid use disorder on immune recovery in HIV-infected people. The study aims to find the best pharmacologic strategy for managing opioid use disease in HIV-infected individuals starting antiretroviral therapy.
Researchers found that mitochondrial fission factor is a key regulator of cancer cell survival and proliferation. The protein's interaction with VDAC1 is critical for tumor cell growth, but disrupting this complex can activate mechanisms of mitochondrial cell death.
A Wistar team is advancing a synthetic DNA technology called DNA-encoded monoclonal antibodies (DMAbs) to combat multidrug-resistant Pseudomonas aeruginosa. The researchers have demonstrated the effectiveness of DMAbs in controlling infection in mice, paving the way for further development and clinical testing.
Researchers at The Wistar Institute have found that ARID1A is essential for telomere cohesion, which helps maintain genomic stability. Inactivation of ARID1A leads to loss of telomere cohesion and selects against gross chromosome alterations.
Scientists found that frequent and sustained semen exposure can change the characteristics of immune cells targeted by HIV-1, reducing susceptibility to future infections. While it does not block infection, repeated semen exposure may promote host resistance, raising new hypotheses for HIV vaccine studies and prevention strategies.
The study found that ARID1A controls the genome-wide positioning of condensin II, a complex regulating gene expression through organizing chromosome structure. This loss affects global gene expression, with broad consequences for cancer types, especially ovarian cancer.
Researchers have developed a novel compound that specifically targets the endoplasmic reticulum stress response in cancer cells, promoting apoptosis and inhibiting tumor growth. The compound can be precisely activated by UV irradiation and emits fluorescence, allowing real-time tracking of its activity.
Researchers at The Wistar Institute have developed a drug candidate for EBV-associated cancers, inhibiting tumor growth in preclinical models. Pharmacological inhibition of EBNA1 had profound effects on gene expression, decreasing EBV DNA copy number and suppressing tumor-promoting pathways.
Researchers at The Wistar Institute have discovered a novel role of NAD+ metabolism in promoting tumor growth and progression in preclinical models of pancreatic cancer. Cellular senescence, a process that stops cells from dividing, can also produce proinflammatory molecules that promote tumor growth.
Researchers discovered that BRAF inhibitors render resistant melanoma cells more sensitive to T cell attack by increasing the expression of a protein called M6PR. This finding suggests that adoptive T cell therapy may be therapeutically useful for patients who have become resistant to BRAF inhibitors.
A novel synthetic DNA vaccine targeting the Mayaro virus envelope protein provides complete protection from disease in preclinical studies. The vaccine induces potent protective and virus-specific immune responses, including neutralizing antibodies and cellular responses.
This study developed a personalized approach to inducing immunity against unique combinations of tumor neoantigens, resulting in higher CD8+ T-cell immunity and delayed tumor growth. The vaccine platform successfully killed tumor cells, slowed tumor progression, and prolonged survival in preclinical models.
Researchers at The Wistar Institute developed novel synthetic DNA-encoded monoclonal antibodies targeting PCSK9, which significantly reduced cholesterol levels in preclinical studies. This approach may provide a less frequent and cost-effective alternative to statins for treating high cholesterol and reducing cardiovascular risk.
Researchers at The Wistar Institute found that the S100A14 protein is expressed at higher levels in these individuals than control donors, activating natural killer cells to defend against HIV. This discovery may lead to novel approaches for prevention of HIV infection by manipulating host immune defense.
Scientists at The Wistar Institute have successfully engineered novel DNA-encoded monoclonal antibodies targeting Zaire Ebolavirus, which offered complete and long-term protection against lethal virus challenges. The study provides a simple, rapid, and reproducible approach for immunization and evaluation of antibody efficacy.
Neutrophils isolated from bone marrow of mouse models and patients with early stage tumors exhibit increased spontaneous migration to tissues and promote tumor cell seeding. These neutrophils lack immunosuppressive characteristics, but display potent ability to spontaneously migrate and facilitate metastasis.
A novel synthetic DNA vaccine offers complete protection from Zaire Ebolavirus infection, with strong immune responses detected one year after the last dose. The vaccine's efficacy and durability support its potential as a new tool for protection against Ebola virus.
Researchers discovered that mutations in the ARID1A gene lead to a molecular switch in the SWI/SNF protein complex, causing an increase in BCL2 expression and promoting tumor cell survival. Inhibiting BCL2 using a small molecule inhibitor kills ovarian cancer cells resistant to EZH2 inhibition.
Researchers at The Wistar Institute developed synthetic DNA-encoded monoclonal antibodies targeting CTLA-4, achieving antitumor activity comparable to traditional monoclonals. The approach stimulates robust CD8+ T-cell infiltration and tumor clearance in mouse models.
Researchers found that loss of HAPLN1 protein in older patients creates a permissive environment for tumor cells to escape and metastasize. The study suggests that targeting HAPLN1 may be a new therapeutic avenue for improving long-term survival in melanoma patients.
A new DNA vaccine targeting the human MAGE-A family of proteins has shown promise in a pre-clinical model of melanoma, inducing a robust immune response and antitumor activity. The vaccine simultaneously targets multiple tumor antigens, overcoming a difficult issue in cancer immunotherapy.
A synthetic DNA vaccine has been shown to produce broad immune responses against diverse H3N2 viruses, which have led to high morbidity and mortality in recent years. The vaccine was found to be more effective than traditional vaccines in protecting mice from lethal influenza A infection.
Researchers found a combination treatment combining a CK2 inhibitor with an immune checkpoint inhibitor dramatically increased antitumor activity, eliminating over 60% of tumors in mouse models. The study suggests manipulating the tumor microenvironment may improve clinical outcomes for cancer patients.
Scientists at The Wistar Institute developed a novel strategy for delivering complex anti-HIV immunoadhesins using synthetic DNA technology, achieving robust and long-term in vivo expression. This breakthrough enables the production of functional eCD4-Ig immunoadhesin with enhanced potency.
INTS13 is a master regulator of gene expression during monocytic differentiation, promoting lineage-specific genes and cell fate determination in hematopoiesis. Depletion of INTS13 disrupts monocytic/macrophagic gene activation, highlighting its indispensable role in monocytic maturation.
Researchers discovered that the tumor suppressor protein ARID1A controls global transcription in ovarian epithelial cells, regulating a large set of genes. Its loss causes dysregulation of important cell functions, including DNA repair and cell proliferation.