A5046547524- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Cancer Genomics and Diagnostics
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Cancer Research and Treatments
- RNA Interference and Gene Delivery
- Hepatitis B Virus Studies
- Robotics and Automated Systems
- Advanced biosensing and bioanalysis techniques
- Bladder and Urothelial Cancer Treatments
- Complement system in diseases
- COVID-19 Clinical Research Studies
- Virus-based gene therapy research
- Influenza Virus Research Studies
- Inflammatory Biomarkers in Disease Prognosis
- Advanced Sensor Technologies Research
- Data-Driven Disease Surveillance
- Sensor Technology and Measurement Systems
- Blood groups and transfusion
- Vaccine Coverage and Hesitancy
- Nanoplatforms for cancer theranostics
- COVID-19 Impact on Reproduction
Icahn School of Medicine at Mount Sinai
2017-2025
Tisch Cancer Institute
2024
Tisch Hospital
2024
Mount Sinai Hospital
2024
Freenome (United States)
2023
This paper describes the sequencing protocol and computational pipeline for PGV-001 personalized vaccine trial. is a therapeutic peptide targeting neoantigens identified from patient tumor samples. Peptides are selected by which identifies mutations tumor/normal exome ranks mutant sequences combination of predicted Class I MHC affinity abundance estimated RNA. The PGV modular consists independently usable tools software libraries. We hope that functionality these may extend beyond specifics...
Early in the pandemic, we designed a SARS-CoV-2 peptide vaccine containing epitope regions optimized for concurrent B cell, CD4
Abstract Immunotherapies like immune checkpoint inhibitors (ICIs) have changed the standard of care for cancer patients, often leading to durable responses. However, many patients remain or become refractory ICIs owing factors such as a lack primed neoantigen-reactive T cells. We developed peptide-based vaccination platform that utilizes fully personalized genome vaccines (PGV) and targets neoantigens predicted by our OpenVax computational pipeline. Here we report results from PGV001 study...
Abstract Therapeutic vaccines targeting mutant tumor antigens (“neoantigens”) are an increasingly popular form of personalized cancer immunotherapy. Vaxrank is a computational tool for selecting neoantigen vaccine peptides from mutations, RNA data, and patient HLA type. freely available at www.github.com/openvax/vaxrank under the Apache 2.0 open source license can also be installed Python Package Index.
Complement-mediated cytotoxicity may act as a selective pressure for tumor overexpression of complement regulators. We hypothesize that the same could lead to alterations at genetic level. find that, when analyzed pathway, mutations in genes occur relatively high frequency and are associated with changes overall survival across number cancer types. Analysis pathways expressed patients poor reveals crosstalk between hypoxia colorectal cancer. The importance this is highlighted by two key...
Abstract There is an urgent need for a vaccine with efficacy against SARS-CoV-2. We hypothesize that peptide vaccines containing epitope regions optimized concurrent B cell, CD4 + T and CD8 cell stimulation would drive both humoral cellular immunity high specificity, potentially avoiding undesired effects such as antibody-dependent enhancement (ADE). Additionally, can be rapidly manufactured in distributed manner. In this study, we combine computational prediction of epitopes, recently...
The impact of pelvic inflammation on prostate cancer (PCa) biology and aggressive phenotype has never been studied. Our study objective was to evaluate the role PCa aggressiveness its association with clinical outcomes in patients following radical prostatectomy (RP). This conducted a retrospective single-institutional consecutive cohort 2278 who underwent robot-assisted laparoscopic (RALP) between 01/2013 10/2019. Data from 2085 were analyzed adverse pathology (AP), defined as Gleason Grade...
597 Background: Most patients (pts) with urothelial cancer (UC) treated immune checkpoint inhibitors (ICIs) do not respond. Given that features associated restrained antitumor immunity and high neoantigen burden have correlated response to ICI, stimulating vaccination is an attractive approach overcome ICI resistance. This study assessed atezolizumab in combination PGV001, a personalized genomic vaccine, the adjuvant metastatic settings. Methods: single-arm pilot (NCT03359239) enrolled pts...
As SARS-CoV-2 variants continue to emerge capable of evading neutralizing antibodies, it has become increasingly important fully understand the breadth and functional profile T cell responses determine their impact on immune surveillance variant strains. Here, sampling healthy individuals, we profiled kinetics polyfunctionality immunity elicited by mRNA vaccination. Modeling anti-spike against ancestral strains suggested that epitope immunodominance cross-reactivity are major predictive...
Abstract Introduction: Immunotherapies such as checkpoint blockade, have demonstrated remarkable clinical efficacy yet a large percentage of patients do not respond, potentially due to paucity pre-existing immune priming against neoantigens. We developed personalized genome vaccine (PGV_001) platform generate neoantigen vaccines targeting each patient’s unique mutanome. Primary objectives the study were determine 1) safety and tolerability; 2) feasibility PGV_001 production administration;...
Abstract This paper describes the sequencing protocol and computational pipeline for PGV-001 personalized vaccine trial. is a therapeutic peptide targeting neoantigens identified from patient tumor samples. Peptides are selected by which identifies mutations tumor/normal exome ranks mutant sequences combination of predicted Class I MHC affinity abundance estimated RNA. The PGV modular consists many independently usable tools software libraries. We draw attention to three particular may be...
Abstract BACKGROUND Glioblastoma (GBM) generates mutation-derived tumor antigens, which arise from somatic variants that result in mutated protein fragments displayed to immune cells. These proteins can provide targets for anti-tumor personalized neoantigen vaccine (PNV) therapy. Combining PNV with Tumor Treating Fields (TTFields), a modality increases survival of GBM patients, is viable option. METHODS In this phase I study (NCT03223103), and TTFields are combined the standard treatment...
Abstract The tumor microenvironment (TME) of glioblastoma (GBM) is populated by cells that foster immunosuppression. Reversing immunosuppression and promoting surveillance T recognize the antigens generated tumor-specific mutations (neoantigens) critical to eliminating cells. In a phase 1 clinical trial newly diagnosed GBM (NCT03223103), patients were treated with personalized neoantigen vaccines (PNV) combined standard care (resection, radiotherapy, temozolomide chemotherapy, TTFields)....
Abstract Background: Urothelial cancer (UC) of the genitourinary tract, most commonly arising from bladder, has historically been a challenging area for development new therapeutics. Immune checkpoint blockade inhibitors (CBIs) induce durable responses only in subset patients with UC, potentially due to lack neoantigen primed T cells. To build on this hypothesis, we designed study evaluate safety and immunogenicity combination treatment atezolizumab PGV-001, personalized genomic vaccine....
e14307 Background: Mutation-derived tumor antigens (MTAs) arise as a direct result of somatic variations that occur during carcinogenesis and can be characterized via genetic sequencing used to identify MTAs. We developed platform for fully-personalized MTA-based vaccine in the adjuvant treatment solid hematological malignancies. Methods: This is single-arm, open label, proof-of-concept phase I study designed test safety immunogenicity Personalized Genomic Vaccine 001 (PGV001) targets up 10...
Abstract Background: The majority of novel cancer immunotherapies rely on adequate priming T cells to tumor-specific neoantigens, which is believed be lacking in patients who do not respond therapy. We developed a personalized genomic vaccine (PGV-001) patient-specific synthetic neoantigen peptides (25 mer),are formulated and administered with multiple types the adjuvant setting (NCT02721043). Methods: This trial enrolled whom had undergone curative-intent surgery (solid tumor patients) or...
Abstract Background: Mutation-derived tumor antigens (MTAs) arise as a result of somatic mutations, such nucleotide substitutions and small insertions/deletions. MTAs can serve specific targets for antitumor therapy, including neoantigen vaccines. The goal vaccination is to help prime T cells recognize tumor-specific mutations. Here we describe phase I trial testing personalized genomic vaccine (PGV-001) in multiple histologies the adjuvant setting (NCT02721043). Methods: This included...
Abstract Glioblastoma (GBM) like other cancers generates mutation-derived tumor antigens (MTA) arising from somatic mutations such as insertions, deletions, nucleotide substitutions and gene fusions. These can be recognized by the immune system, providing a specific target for antitumor therapy. The use of TTFields, modality that utilizes low intensity electric fields disrupt cell division, increases progression-free survival overall in newly diagnosed GBM. Among several mechanisms action,...