A5049294342- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Protein Degradation and Inhibitors
- Melanoma and MAPK Pathways
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Cutaneous Melanoma Detection and Management
- Chemokine receptors and signaling
- Hepatitis B Virus Studies
- Reproductive System and Pregnancy
- Glioma Diagnosis and Treatment
- Glycosylation and Glycoproteins Research
- Hepatitis C virus research
- Biomedical Ethics and Regulation
- Cancer Genomics and Diagnostics
- Escherichia coli research studies
- Liver Disease Diagnosis and Treatment
- Click Chemistry and Applications
- Advancements in Transdermal Drug Delivery
- Complement system in diseases
- Biosimilars and Bioanalytical Methods
University of Virginia
2014-2024
University of Virginia Health System
2004-2024
University of Virginia Cancer Center
2021-2022
Christ Hospital
2013
UPMC Hillman Cancer Center
2013
Dana-Farber Cancer Institute
2013
Christ Hospital
2013
Fox Chase Cancer Center
2009-2013
Johns Hopkins University
2013
Center for Open Science
2013
Hepatitis C virus (HCV) is an important human pathogen that remarkably efficient at establishing persistent infection. The HCV core protein the first expressed during early phase of Our previous work demonstrated suppresses host immune responses, including anti-viral cytotoxic T-lymphocyte responses in a murine model. To investigate mechanism core-mediated immunosuppression, we searched for proteins capable associating with using yeast two-hybrid system. Using as bait, screened T...
To determine clinical and immunologic responses to a multipeptide melanoma vaccine regimen, randomized phase II trial was performed.Twenty-six patients with advanced were randomly assigned vaccination mixture of four gp100 tyrosinase peptides restricted by HLA-A1, HLA-A2, HLA-A3, plus tetanus helper peptide, either in an emulsion granulocyte-macrophage colony-stimulating factor (GM-CSF) Montanide ISA-51 adjuvant (Seppic Inc, Fairfield, NJ), or pulsed on monocyte-derived dendritic cells...
Abstract Purpose: Granulocyte/macrophage colony-stimulating factor (GM-CSF) administered locally together with vaccines can augment T-cell responses in animal models. Human experience has been limited to small and uncontrolled trials. Thus, a multicenter randomized phase II trial was done determine whether local administration of GM-CSF augments immunogenicity multipeptide vaccine. It also assessed one versus two vaccine sites. Experimental Design: One hundred twenty-one eligible patients...
Abstract Purpose: Human melanoma cells express shared antigens recognized by CD8+ T lymphocytes, the most common of which are melanocytic differentiation proteins and cancer-testis antigens. However, peptide vaccines for usually target only one or two MHC class I–associated Because melanomas commonly evade immune recognition selective antigen loss, optimization may require development more complex multipeptide vaccines. Experimental Design: In a prospective randomized clinical trial, we have...
Purpose This multicenter randomized trial was designed to test whether melanoma-associated helper peptides augment CD8 + T-cell responses a melanoma vaccine and cyclophosphamide (CY) pretreatment augments CD4 or that vaccine. Patients Methods In all, 167 eligible patients with resected stage IIB IV were randomly assigned four vaccination study arms. vaccinated 12 class I major histocompatibility complex–restricted (12MP) stimulate T cells receive tetanus peptide mixture of six (6MHP) cells....
Abstract Purpose: This multicenter randomized trial was designed to evaluate whether melanoma helper peptides augment cytotoxic T lymphocyte (CTL) responses a vaccine and improve clinical outcome in patients with advanced melanoma. Experimental Design: One hundred seventy-five measurable stage IV were enrolled into 4 treatment groups, vaccinated 12 MHC class I-restricted stimulate CTL (12MP, group A), plus tetanus peptide (group B), or mixture of 6 (6MHP, C) lymphocytes (HTL), (6MHP) alone...
Abstract The critical roles of CD4 + T cells have been understudied for cancer vaccines. Here we report long-term clinical outcomes a randomized multicenter phase II trial (NCT00118274), where patients with high-risk melanoma received multipeptide vaccine targeting CD8 (12MP) and were to receive either two vaccines (helper) cells: 6MHP (6 melanoma-specific helper peptides), or tet (a nonspecific peptide from tetanus toxoid). Cyclophosphamide (Cy) pre-treatment was also assessed. Primary cell...
A phase II trial was performed to test whether systemic low-dose interleukin-2 (IL-2) augments T-cell immune responses a multipeptide melanoma vaccine. Forty patients with resected stage IIB-IV were randomly assigned vaccination four gp100- and tyrosinase-derived peptides restricted by human leukocyte antigen (HLA) -A1, HLA-A2, HLA-A3, tetanus helper peptide plus IL-2 administered daily either beginning day 7 (group 1), or 28 2).T-cell assessed an interferon gamma ELIspot assay in peripheral...
Abstract Twelve peptides derived from melanocyte differentiation proteins and cancer-testis Ags were combined administered in a single mixture to patients with resected stage IIB, III, or IV melanoma. Five of the 12 included this had not previously been evaluated for their immunogenicity vivo following vaccination. We report study that at least three these five (MAGE-A196–104, MAGE-A10254–262, gp100614–622) are immunogenic when GM-CSF Montanide ISA-51 adjuvant. T cells secreting IFN-γ...
A phase I/II trial was performed to evaluate the safety and immunogenicity of a novel melanoma vaccine comprising six melanoma-associated peptides defined as antigenic targets for melanoma-reactive helper T cells. Source proteins these include MAGE proteins, MART-1/MelanA, gp100, tyrosinase.Thirty-nine patients with stage IIIB IV were vaccinated this six-peptide mixture weekly at three dose levels, preceding I escalation subsequent random assignment among levels. Helper T-lymphocyte...
Nine participants with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, who were human leukocyte antigen (HLA)-A1+, HLA-A2+, HLA-A3+, eligible to enroll in a phase 1 study designed assess the safety and immunogenicity of peptide-based vaccine. Participants received 5 class I major histocompatibility complex-restricted synthetic peptides derived from multiple ovarian cancer-associated proteins plus II helper peptide tetanus toxoid protein. The vaccines administered...
Clinical trials of immunologic therapies provide opportunities to study the cellular and molecular effects those may permit identification biomarkers response. When are performed at multiple centers, transport storage clinical specimens become important variables that affect lymphocyte viability function in blood tissue specimens. The effect temperature during shipment peripheral on subsequent processing, recovery, lymphocytes is understudied represents focus this study.Peripheral samples (n...
<h3>Background</h3> Cancer vaccines require adjuvants to induce effective immune responses; however, there is no consensus on optimal adjuvants. We hypothesized that toll-like receptor (TLR)3 agonist polyICLC or TLR4 lipopolysaccharide (LPS), combined with CD4 T cell activation, would support strong and durable CD8<sup>+</sup> responses, whereas addition of an incomplete Freund's adjuvant (IFA) reduce magnitude persistence responses. <h3>Patients methods</h3> Participants resected stage...
Background Phosphorylated peptides presented by MHC molecules represent a new class of neoantigens expressed on cancer cells and recognized CD8 T-cells. These are promising targets for immunotherapy. Previous work identified an HLA-A*0201-restricted phosphopeptide from insulin receptor substrate 2 (pIRS2) as one such target. The purpose this study was to characterize second phosphopeptide, breast antiestrogen resistance 3 (BCAR3), evaluate safety immunogenicity novel immunotherapic vaccine...
We have previously shown that within tumors, recombinant interleukin-2 (rIL-2, aldesleukin) consistently activates tumor-associated macrophages and upregulates IFN-stimulated genes while inducing minimal migration, activation, or proliferation of T cells. These effects are independent tumor response to treatment. Here, we prospectively evaluated transcriptional alterations induced by rIL-2 in peripheral blood mononuclear cells (PBMC) melanoma metastases.We gene expression changes serially...
<h3>Background</h3> Breast cancer remains a leading cause of death worldwide. There is evidence that immunotherapy may play role in the eradication residual disease. Peptide vaccines for are capable durable immune memory, but alone have shown sparse clinical activity against breast to date. Toll-like receptor (TLR) agonists and helper peptides excellent adjuvants vaccine they examined this human trial. <h3>Methods</h3> A consisting 9 MHC class I-restricted cancer-associated (from MAGE-A1,...
Background We performed a clinical trial to evaluate safety and immunogenicity of novel long peptide vaccine administered in combinations incomplete Freund’s adjuvant (IFA) agonists for TLR3 (polyICLC) TLR7/8 (resiquimod). hypothesized that T cell responses minimal epitope peptides (MEPs) within the would be enhanced compared with prior vaccines MEP themselves TLR agonists, IFA alone. Methods Participants resected stage IIB-IV melanoma were vaccinated seven (LPV7) from tyrosinase, gp100,...
ABSTRACT Hepatitis C virus (HCV) is remarkably efficient in establishing persistent infection, possibly mediated by an impaired immune response to HCV infection. There compelling evidence that can infect cells, such as macrophages, B and T cells. It has been previously reported core, the first protein expressed during early phase of viral contains immunomodulatory function suppressing host responses. This altered cells caused infection may explain ineffective HCV. To further characterize...
A CTEP-sponsored phase II trial was conducted to evaluate safety and clinical activity of combination therapy with CCI-779 (temsirolimus) bevacizumab in patients advanced melanoma.Patients unresectable stage III IV melanoma were treated intravenously temsirolimus 25 mg weekly 10 every 2 weeks. Adverse events recorded using CTCAE v3.0. Tumor response assessed by Response Evaluation Criteria Solid Tumors overall survival recorded. Correlative studies measured protein kinases histology tumor...
Cancer vaccines have not been optimized. They depend on adjuvants to create an immunogenic microenvironment for antigen presentation. However, remarkably little is understood about cellular and molecular changes induced by these in the vaccine microenvironment. We hypothesized that vaccination induces dendritic cell (DC) activation dermal but regulatory processes may also limit effectiveness of repeated vaccination. evaluated biopsies from immunization sites 2 clinical trials melanoma...