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Articles by Immunotherapy Programs
Neoantigen DNA vaccines are safe, feasible, and induce neoantigen-specific immune responses in triple-negative breast cancer patients - Genome Medicine
Neoantigen DNA vaccines were designed and manufactured while subjects underwent standard therapy (Fig. 1A). Tumor RNA sequencing (using cDNA capture) was performed to assess the expression of somatic mutations. After completion of adjuvant therapy, subjects received three neoantigen DNA vaccinations via electroporation at monthly intervals. A total of 35 patients with TNBC consented to the trial (Fig. 1B).
Influenza vaccination stimulates maturation of the human T follicular helper cell response - Nature Immunology
Abstract The differentiation and specificity of human CD4+ T follicular helper cells (TFH cells) after influenza vaccination have been poorly defined. Here we profiled blood and draining lymph node (LN) samples from human volunteers for over 2 years after two influenza vaccines were administered 1 year apart to define the evolution of the CD4+ TFH cell response. The first vaccination induced an increase in the frequency of circulating TFH (cTFH) and LN TFH cells at week 1 postvaccination.
CXCL16-dependent scavenging of oxidized lipids by islet macrophages promotes differentiation of pathogenic CD8+ T cells in diabetic autoimmunity
Highlights • CXCL16 in islet resident macrophages is crucial for OxLDL clearance in islets • Cxcl16 deletion in NOD mice suppresses T1D via an islet-specific mechanism • OxLDL exposure diminishes intra-islet transitory CD8+ T cells through ferroptosis • PD-1 blockade rescues transitory CD8+ T cells and reverses diabetes resistance Summary The pancreatic islet microenvironment is highly oxidative, rendering β cells vulnerable to autoinflammatory insults.
The many ways in which alphaviruses bind to cells
Highlights Proteinaceous receptors bind distinct sites of the alphavirus glycoprotein to mediate efficient cellular entry. The cleft formed by E1–E2 heterodimers is utilized by the mammalian MXRA8 to bind Chikungunya virus (CHIKV) and LDLRAD3 to bind Venezuelan equine encephalitis virus (VEEV). VLDLR binds Semliki forest virus (SFV) outside of the cleft at the fivefold and twofold icosahedral vertices, resulting in an avid interaction involving multiple lipoprotein A (LA) domains with E1-DIII.
Prostate cancer immunotherapy: Improving clinical outcomes with a multi-pronged approach
Summary Cancer immunotherapy has gained traction in recent years owing to remarkable tumor clearance in some patients. Despite the notable success of immune checkpoint blockade (ICB) in multiple malignancies, engagement of the immune system for targeted prostate cancer (PCa) therapy is still in its infancy. Multiple factors contribute to limited response, including the heterogeneity of PCa, the cold tumor microenvironment, and a low number of neoantigens.
An antiviral role for TRIM14 in Ebola virus infection
Ebola virus (EBOV) is a highly pathogenic virus that encodes seven multifunctional structural proteins. Multiple host factors have been reported to interact with the EBOV proteins. Here, we found that Tripartite motif-containing 14 (TRIM14), an interferon-stimulated gene that mediates cellular signaling pathways associated with type I interferon and inflammatory cytokine production, interacts with EBOV nucleoprotein (NP) to enhance IFN-β and NF-κB promotor activation.
Persons with HIV Develop Spike-Specific Lymph Node Germinal Center Responses following SARS-CoV-2 Vaccination
6 Geretti , A. M. , A. J. Stockdale , S. H. Kelly , M. Cevik , S. Collins , L. Waters , G. Villa , A. Docherty , E. M. Harrison , L. Turtle , et al. 2021 . Outcomes of coronavirus disease 2019 (COVID-19) related hospitalization among people with human immunodeficiency virus (HIV) in the ISARIC World Health Organization (WHO) clinical characterization protocol (UK): a prospective observational study . Clin. Infect. Dis. 73 : e2095 – e2106 .
Emil R. Unanue (1934-2022)
Main text Two years after being diagnosed with glioblastoma, Emil Raphael Unanue passed away on December 16, 2022, surrounded by his family. With his passing, immunology lost a giant. Emil Unanue’s contributions to immunology and his career path are legendary, as detailed by some of our other colleagues elsewhere, but here are some highlights: Emil was born in 1934 and raised in Havana, Cuba.
Long Live the Plasma Cell: The Basis of Sustained Humoral Immunity
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Immunotherapy booster produces 10,000 times more cancer-fighting cells Original
Researchers at Washington University in St. Louis have found that adding a booster protein can significantly improve the outcome of cancer immunotherapy. Tests in mice showed the protein produced 10,000 times more immune cells, with all mice surviving the entire experiment. Our immune system is a powerful line of defense against disease, including cancer, but sometimes even it could use a hand.
Single-cell profiling of human dura and meningioma reveals cellular meningeal landscape and insights into meningioma immune response - Genome Medicine
Experimental design The objective of this study was to characterize the cellular composition of human dura and meningioma at a single-cell resolution. The study design involved performing 3′ and 5′ single-cell RNA sequencing, with V(D) J enrichment for select samples, in addition to imaging mass cytometry and immunohistochemistry. Patient recruitment and sample collection Adult patients undergoing neurosurgical intervention at Barnes-Jewish Hospital were screened.
Germinal centre-driven maturation of B cell response to mRNA vaccination - Nature
Abstract Germinal centres (GC) are lymphoid structures where B cells acquire affinity-enhancing somatic hypermutations (SHM), with surviving clones differentiating into memory B cells (MBCs) and long-lived bone marrow plasma cells (BMPCs)1–5. SARS-CoV-2 mRNA vaccination induces a persistent GC response that lasts for at least six months in humans6–8. The fate of responding GC B cells as well as the functional consequences of such persistence have not been elucidated.
An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies - Nature Medicine
Abstract The emergence of the highly transmissible B.1.1.529 Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is concerning for antibody countermeasure efficacy because of the number of mutations in the spike protein.
The germinal centre B cell response to SARS-CoV-2 - Nature Reviews Immunology
Abstract The germinal centre (GC) response is critical for the generation of affinity-matured plasma cells and memory B cells capable of mediating long-term protective immunity. Understanding whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination elicits a GC response has profound implications for the capacity of responding B cells to contribute to protection against infection. However, direct assessment of the GC response in humans remains a major challenge.
Structure of Venezuelan equine encephalitis virus in complex with the LDLRAD3 receptor - Nature
Abstract LDLRAD3 is a recently defined attachment and entry receptor for Venezuelan equine encephalitis virus (VEEV)1, a New World alphavirus that causes severe neurological disease in humans. Here we present near-atomic-resolution cryo-electron microscopy reconstructions of VEEV virus-like particles alone and in a complex with the ectodomains of LDLRAD3.
Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail - Nature Microbiology
Abstract Understanding the molecular basis for immune recognition of SARS-CoV-2 spike glycoprotein antigenic sites will inform the development of improved therapeutics. We determined the structures of two human monoclonal antibodies–AZD8895 and AZD1061–which form the basis of the investigational antibody cocktail AZD7442, in complex with the receptor-binding domain (RBD) of SARS-CoV-2 to define the genetic and structural basis of neutralization.
SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans - Nature
Abstract Long-lived bone marrow plasma cells (BMPCs) are a persistent and essential source of protective antibodies1,2,3,4,5,6,7. Individuals who have recovered from COVID-19 have a substantially lower risk of reinfection with SARS-CoV-28,9,10.
Potently neutralizing and protective human antibodies against SARS-CoV-2 - Nature
Abstract The ongoing pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major threat to global health1 and the medical countermeasures available so far are limited2,3. Moreover, we currently lack a thorough understanding of the mechanisms of humoral immunity to SARS-CoV-24.
The Challenges of Vaccine Development against a New Virus during a Pandemic
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA
Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19
Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19 Free http://orcid.org/0000-0001-5045-5255Maximilian F Konig1, http://orcid.org/0000-0003-4074-0516Alfred HJ Kim2,3,4, Marc H Scheetz5,6, Elizabeth R Graef7, Jean W Liew8, Julia Simard9, http://orcid.org/0000-0002-8411-7972Pedro M Machado10,11,12, Milena Gianfrancesco13, Jinoos Yazdany13, Daman Langguth14, http://orcid.org/0000-0002-3156-3418Philip C Robinson15 On...
The continued threat of emerging flaviviruses
Abstract Flaviviruses are vector-borne RNA viruses that can emerge unexpectedly in human populations and cause a spectrum of potentially severe diseases including hepatitis, vascular shock syndrome, encephalitis, acute flaccid paralysis, congenital abnormalities and fetal death. This epidemiological pattern has occurred numerous times during the last 70 years, including epidemics of dengue virus and West Nile virus, and the most recent explosive epidemic of Zika virus in the Americas.
Dengue Antibodies, then Zika: A Fatal Sequence in Mice
To use the Enhanced view of this article, please enable JavaScript on in your browser and refresh the page. PreviewDengue Antibodies, then Zika: A Fatal Sequence in Mice Jonathan J. MinerxJonathan J.
Immune-Mediated Protection and Pathogenesis of Chikungunya Virus
Chikungunya virus (CHIKV) is a re-emerging alphavirus that causes debilitating acute and chronic arthritis. Infection by CHIKV induces a robust immune response that is characterized by production of type I IFNs, recruitment of innate and adaptive immune cells, and development of neutralizing Abs.
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