A5005942637- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- vaccines and immunoinformatics approaches
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Influenza Virus Research Studies
- RNA Research and Splicing
- Lung Cancer Treatments and Mutations
- Cancer Diagnosis and Treatment
- T-cell and B-cell Immunology
- Lung Cancer Diagnosis and Treatment
- RNA modifications and cancer
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Genomics and Chromatin Dynamics
- Radiomics and Machine Learning in Medical Imaging
- RNA and protein synthesis mechanisms
- Cancer Research and Treatments
- Head and Neck Cancer Studies
- Melanoma and MAPK Pathways
- Silk-based biomaterials and applications
- Lymphoma Diagnosis and Treatment
- T-cell and Retrovirus Studies
- Viral-associated cancers and disorders
Baylor Scott & White Health
2025
University Hospitals of North Midlands NHS Trust
2015-2024
Moderna Therapeutics (United States)
2023-2024
BioNTech (United States)
2020-2023
Royal Stoke University Hospital
2014-2020
Ribon Therapeutics (United States)
2018
Sanofi (United States)
2017
Harvard University
2008-2015
Boston Children's Hospital
2009-2012
University of Leicester
2008
Abstract mRNA-4157 (V940) is an individualized neoantigen therapy targeting up to 34 patient-specific tumor neoantigens induce T-cell responses and potentiate antitumor activity. We report mechanistic insights into the immunogenicity of via characterization from first-in-human, phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non–small cell lung cancer (Part A: 1-mg mRNA-4157, n = 4) or cutaneous melanoma D: + 200-mg pembrolizumab, 12). Safety, tolerability, were assessed....
Tumor cells display fundamental changes in metabolism and nutrient uptake order to utilize additional sources meet their enhanced bioenergetic requirements. Glutamine (Gln) is one such that rapidly taken up by tumor fulfill this increased metabolic demand. A vital step the catabolism of glutamine its conversion glutamate mitochondrial enzyme glutaminase (GLS). This study has identified GLS a potential therapeutic target breast cancer, specifically basal subtype exhibits deregulated...
Abstract Background The ongoing COVID-19 pandemic has created an urgency to identify novel vaccine targets for protective immunity against SARS-CoV-2. Early reports roles both humoral and cell-mediated Methods We leveraged our bioinformatics binding prediction tools human leukocyte antigen (HLA)-I HLA-II alleles that were developed using mass spectrometry-based profiling of individual HLA-I predict peptide diverse allele sets. applied these predictors viral genomes from the Coronaviridae...
T cells use highly diverse receptors (TCRs) to identify tumor presenting neoantigens arising from genetic mutations and establish anti-tumor activity. Immunotherapy harnessing neoantigen-specific target tumors has emerged as a promising clinical approach. To assess whether comprehensive peripheral mononuclear blood cell analysis predicts responses personalized neoantigen cancer vaccine combined with anti-PD-1 therapy, we characterize the TCR repertoires B frequencies in 21 patients...
Abstract Introduction: mRNA-4157 is a novel mRNA-based individualized neoantigen therapy (INT) designed to enhance endogenous antitumor T-cell responses by targeting unique patient-specific tumor mutations. In the phase 2 mRNA-4157-P201 (KEYNOTE-942) trial, patients with completely resected high-risk stage IIIB-IV melanoma receiving + pembrolizumab (pembro) showed prolonged recurrence-free survival (RFS) and distant metastasis-free (DMFS) versus those pembro alone (Weber JS, et al. Lancet...
Significance Clonal expansion of antigen-specific B cells during an immune response is necessary for effective antibody production. must integrate signals from their clonally restricted B-cell antigen receptor (BCR) and nonclonal coreceptors that provide contextual cues to the nature antigen. How this accomplished unclear. We found require expression BCR mitogenic responses triggered by recognize innate or T-cell-derived signals. The signaling pathway used license coreceptor-induced...
Abstract Background The ongoing COVID-19 pandemic has created an urgency to identify novel vaccine targets for protective immunity against SARS-CoV-2. Consistent with observations SARS-CoV, a closely related coronavirus responsible the 2003 SARS outbreak, early reports role both humoral and cell-mediated CoV-2. Methods In this study, we leveraged HLA-I HLA-II T cell epitope prediction tools from RECON® (Real-time Epitope Computation ONcology), our bioinformatic pipeline that was developed...
CD4+ T cells are critical to the immune system and perform multiple functions; therefore, their identification characterization crucial better understanding in both health disease states. However, current methods rarely preserve ex vivo phenotype, thus limiting our of functions. Here we introduce a flexible, rapid, robust platform for cell identification. By combining MHCII allele purification, allele-independent peptide loading, multiplexed flow cytometry technologies, can enable...
Abstract Introduction: In HPV- HNSCC, limited durable clinical responses to PD1/PD-L1 blockade may be due diminished effector cytolytic activity and clonal diversity.1-4 mRNA-4157 is a novel mRNA-based INT that encodes up 34 neoantigens inducing specific antitumor T-cell activation; with pembro have been shown in melanoma.5 We assessed + unresectable, metastatic HNSCC the Phase 1 mRNA-4157-P101/KEYNOTE-603 study (NCT03313778). Methods: Part C of this enrolled ≥18-year-old patients (pts)...
Background High-risk human papillomavirus (HPV) is a primary cause of an increasing number oropharyngeal squamous cell carcinomas (OPSCCs). The viral etiology these cancers provides the opportunity for antigen-directed therapies that are restricted in scope compared with without components. However, specific virally-encoded epitopes and their corresponding immune responses not fully defined. Methods To understand OPSCC landscape, we conducted comprehensive single-cell analysis HPV16+ HPV33+...
Delivery of small-interfering RNA (siRNA) has been great interest in the past decade for effective gene silencing. To overcome synthetic and regulatory challenges posed by nanoparticle-mediated siRNA delivery, antibody-siRNA conjugate (ARC) platform is emerging as a potential delivery system suitable clinical translation. Herein, we have developed technology based on ARC stable called Gelatin-Antibody System (GADS). In GADS, positively charged gelatin acts linker between enables endosomal...
<p>Supplementary methods.</p>