A5049996758- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Toxoplasma gondii Research Studies
- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- Ubiquitin and proteasome pathways
- SARS-CoV-2 and COVID-19 Research
- Peptidase Inhibition and Analysis
- Hepatitis B Virus Studies
- Virus-based gene therapy research
- Bacterial Genetics and Biotechnology
- Viral gastroenteritis research and epidemiology
- RNA and protein synthesis mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Renal Transplantation Outcomes and Treatments
- Viral Infections and Outbreaks Research
ExpreS2ion Biotechnologies (Denmark)
2023-2025
Technical University of Denmark
2014-2016
La Jolla Institute for Immunology
2016
National University of General San Martín
2015
Abstract HLA class I–binding predictions are widely used to identify candidate peptide targets of human CD8+ T cell responses. Many such approaches focus exclusively on a limited range lengths, typically 9 aa and sometimes 9–10 aa, despite multiple examples dominant epitopes other lengths. In this study, we examined whether epitope can be improved by incorporating the natural length distribution I ligands. We found that, although different alleles have diverse length-binding preferences,...
Abstract Motivation: Numerous in silico methods predicting peptide binding to major histocompatibility complex (MHC) class I molecules have been developed over the last decades. However, multitude of available prediction tools makes it non-trivial for end-user select which tool use a given task. To provide solid basis on compare different tools, we here describe framework automated benchmarking peptide-MHC tools. The runs weekly benchmarks data that are newly entered into Immune Epitope...
Abstract Motivation Computational methods for the prediction of peptide-MHC binding have become an integral and essential component candidate selection in experimental T cell epitope discovery studies. The sheer amount published methods—and often discordant reports on their performance—poses a considerable quandary to experimentalist who needs choose best tool research. Results With goal provide unbiased, transparent evaluation state-of-the-art field, we created automated platform benchmark...
HLA class I presentation of pathogen-derived peptide ligands is essential for CD8+ T-cell recognition Toxoplasma gondii infected cells. Currently, little data exist pertaining to peptides that are presented after T. infection. Herein we purify HLA-A*02:01 complexes from cells and characterize the using LCMS. We identify 195 encoded originating both secreted cytoplasmic proteins. Surprisingly, significantly longer than uninfected host ligands, these maintain a canonical N-terminal binding...
The majority of neoantigens arise from unique mutations that are not shared between individual patients, making neoantigen-directed immunotherapy a fully personalized treatment approach. Novel technical advances in next-generation sequencing tumor samples and artificial intelligence (AI) allow fast systematic prediction neoantigens. This study investigates feasibility, safety, immunity, anti-tumor potential the peptide-based neoantigen vaccine, EVX-01, including novel CD8+ T-cell inducing...
Personalized cancer vaccines (PCVs) largely leverage neoantigens arising from somatic mutations, limiting their application to patients with relatively high tumor mutational burden (TMB). This underscores the need for alternative antigens design PCVs low TMB cancers. To this end, we substantiate endogenous retroviral elements (EVEs) as through large-scale genomic analyses of healthy tissues and solid These revealed that breadth EVE expression in tumors stratify checkpoint inhibitor-treated...
Abstract Recent findings have positioned tumor mutation-derived neoepitopes as attractive targets for cancer immunotherapy. Cancer vaccines that deliver via various vaccine formulations demonstrated promising preliminary results in patients and animal models. In the presented work, we assessed ability of plasmid DNA to confer neoepitope immunogenicity anti-tumor effect two murine syngeneic We vaccination led immunity CT26 B16F10 models, with long-lasting presence neoepitope-specific T-cell...
Despite improvements made with checkpoint inhibitor (CPI) therapy, a need for new approaches to improve outcomes patients unresectable or metastatic melanoma remains. EVX-01, personalized neoepitope vaccine, combined pembrolizumab treatment, holds the potential fulfill this need. Here we present rationale and novel design behind KEYNOTE – D36 trial: an open label, single arm, phase II trial aiming establish clinical proof of concept evaluate safety EVX-01 in combination CPI naive melanoma....
Identifying the specific human leukocyte antigen (HLA) allele combination of an individual is crucial in organ donation, risk assessment autoimmune and infectious diseases cancer immunotherapy. However, due to high genetic polymorphism this region, HLA typing requires specialized methods. We investigated performance five next-generation sequencing (NGS) based tools with a non-restricted license namely HLA*LA, Optitype, HISAT-genotype, Kourami STC-Seq. This evaluation was done for loci,...
Abstract The features of peptide antigens that contribute to their immunogenicity are not well understood. Although the stability peptide-MHC (pMHC) is known be important, current assays assess this interaction only for peptides in isolation and context natural antigen processing presentation. Here, we present a method provides comprehensive unbiased measure pMHC thousands individual ligands detected simultaneously by mass spectrometry (MS). allows rapid assessment intra-allelic...
Peptides that bind to and are presented by MHC class I II molecules collectively make up the immunopeptidome. In context of vaccine development, an understanding immunopeptidome is essential, much effort has been dedicated its accurate cost-effective identification. Current state-of-the-art methods mainly comprise in silico tools for predicting binding, which strongly correlated with peptide immunogenicity. However, only a small proportion peptides are, fact, immunogenic, substantial work...
9561 Background: Personalized vaccines, targeting mutation-derived neoantigens (neoAg), represent a promising frontier in cancer immunotherapy. Here, we characterize the vaccine-induced immune response seven melanoma patients treated with AI-generated personalized vaccine, EVX-01, ongoing single arm multicenter trial (NCT05309421). Data from an additional five will be available at time of presentation. Methods: Tumor-specific neoAgs were identified and selected using proprietary vaccine...
Abstract Tumor mutations giving rise to neoantigens have recently emerged as promising targets for cancer immunotherapy. Vaccines delivering tumor-specific demonstrated favorable efficacy and safety results in numerous preclinical early clinical studies. However, selecting therapeutically relevant amongst the myriad of has proven challenging. To overcome this, we developed a proprietary AI-based target discovery platform, PIONEER, with enhanced predictive performance increased precision. The...
<h3>Background</h3> EVX-02, a personalized neoantigen DNA vaccine, was assessed in combination with an anti-PD-1 therapy (nivolumab) patients fully resected melanoma and at high risk of disease recurrence. The EVX-02 vaccines were designed by Evaxion's proprietary AI platform, PIONEER, based on the unique mutational profile each tumor patient's HLA type. PIONEER identifies cancer-specific mutations analyzing differences sequences healthy sample. non-synonymous subset these is then further...
SUMMARY Personalized cancer vaccines (PCVs) largely leverage neoantigens arising from somatic mutations limiting their application to patients with relatively high tumor mutational burden (TMB). This underscores the need for alternative antigens design PCVs low TMB cancers. To this end, we substantiate endogenous retroviral elements (EVEs) as through large-scale genomic analyses of healthy tissues and solid These revealed that breadth EVE expression in tumors stratify checkpoint inhibitor...
The human leukocyte antigen (HLA) system is a group of genes coding for proteins that are central to the adaptive immune and identifying specific HLA allele combination patient relevant in organ donation, risk assessment autoimmune infectious diseases cancer immunotherapy. However, due high genetic polymorphism this region, typing requires specialized methods. We investigated performance five next-generation-sequencing (NGS) based tools with non-restricted license namely HLA*LA, Optitype,...
<h3>Background</h3> Neoantigens derived from cancer-specific mutations are currently being utilized as targets in personalized cancer vaccine treatments. Here, we characterize the neoantigen-specific reactivity and clinical response five patients treated with an AI generated therapeutic (EVX-01)<sup>1</sup> ongoing melanoma single-arm open-label multi-center phase II trial (NCT05309421). <h3>Methods</h3> The proprietary PIONEER<sup>TM</sup> platform for identification selection of...