A5088104084- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Poxvirus research and outbreaks
- CAR-T cell therapy research
- Herpesvirus Infections and Treatments
- Cancer Research and Treatments
- Immune Cell Function and Interaction
- vaccines and immunoinformatics approaches
- Immune cells in cancer
- Hepatitis B Virus Studies
- interferon and immune responses
- Viral Infectious Diseases and Gene Expression in Insects
- Respiratory viral infections research
- T-cell and B-cell Immunology
- Bacillus and Francisella bacterial research
- Influenza Virus Research Studies
- Pneumonia and Respiratory Infections
- Phagocytosis and Immune Regulation
- Nanoplatforms for cancer theranostics
- Viral Infections and Outbreaks Research
- Cell Adhesion Molecules Research
- Viral gastroenteritis research and epidemiology
Dalhousie University
2003-2021
Immunovaccine (Canada)
2012-2019
Nova Scotia Health Authority
2017-2018
Izaak Walton Killam Health Centre
2017-2018
University of Ottawa
2010-2012
Ottawa Hospital
2010-2012
Ottawa Hospital Research Institute
2010-2012
Western University
2005-2009
Robarts Clinical Trials
2007
Memorial University of Newfoundland
2002
We demonstrate that the susceptibility of human cancer cells to be infected and killed by an oncolytic poxvirus, myxoma virus (MV), is related basal level endogenous phosphorylated Akt. further nonpermissive tumor will switch from resistant susceptible for MV infection after expression ectopically active Akt (Myr-Akt) permissive can rendered blocking activation with a dominant-negative inhibitor Finally, involves formation complex between viral host range ankyrin-repeat protein, M-T5,...
Oncolytic viruses (OVs) have been engineered or selected for cancer cell-specific infection however, we found that following intravenous administration of vesicular stomatitis virus (VSV), tumor cell killing rapidly extends far beyond the initial sites infection. We show here first time VSV directly infects and destroys vasculature in vivo but leaves normal intact. Three-dimensional (3D) reconstruction infected tumors revealed majority mass lacks significant blood flow contrast to uninfected...
A major barrier to all oncolytic viruses (OVs) in clinical development is cellular innate immunity, which variably active a spectrum of human malignancies. To overcome the heterogeneity tumor response, we combined complementary OVs that attack cancers distinct ways improve therapeutic outcome. Two genetically viruses, vesicular stomatitis virus (VSV) and vaccinia (VV), were used eliminate risk recombination. The combination was tested variety types vitro, immunodeficient immunocompetent...
We have shown previously the oncolytic potential of myxoma virus in a murine xenograft model human glioma. Here, we show that used alone or combination with rapamycin is effective and safe when experimental models medulloblastoma vitro vivo. Nine 10 cell lines tested were susceptible to lethal infection, pretreatment cells increased extent oncolysis. Intratumoral injection live compared control inactivated prolonged survival D341 Daoy orthotopic mouse [D341 median survival: 21 versus 12.5...
DepoVax™ is an innovative and strongly immunogenic vaccine platform. Survivin highly expressed in many tumor types has reported prognostic value. To generate tumor-specific immune response, a novel cancer was formulated DepoVax platform (DPX-Survivac) using survivin HLA class I peptides. Safety potency of DPX-Survivac tested combination with immune-modulator metronomic cyclophosphamide ovarian patients. All the patients receiving therapy produced antigen-specific responses; higher dose...
DepoVax is a novel non-emulsion depot-forming vaccine platform with the capacity to significantly enhance immunogenicity of peptide cancer antigens. Naturally processed HLA-A2 restricted peptides presented by breast, ovarian and prostate cells were used as antigens create therapeutic vaccine, DPX-0907.A phase I clinical study was designed examine safety immune activating potential DPX-0907 in advanced stage patients. A total 23 late patients recruited divided into two dose/volume cohorts...
Myxoma virus is a rabbit-specific poxvirus pathogen that also exhibits unique tropism for human tumor cells and dramatically oncolytic cancer xenografts. Most cell lines tested are permissive myxoma infection in fashion intimately tied to the activation state of Akt kinase. A host range factor virus, M-T5, directly interacts with mediates tropism. mTOR regulator growth metabolism downstream specifically inhibited by rapamycin. We report treatment nonpermissive lines, which normally restrict...
Myxoma virus (MV) is a rabbit-specific poxvirus, whose unexpected tropism to human cancer cells has led studies exploring its potential use in oncolytic therapy. MV infects wide range of vitro, manner intricately linked the cellular activation Akt kinase. also been successfully used for treating glioma xenografts immunodeficient mice. This study examines effectiveness primary and metastatic mouse tumors immunocompetent C57BL6 We have found that several tumor cell lines, including B16...
Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, goal this study is determine whether HDI can also enhance potency these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested Trichostatin A (TSA) was found potently spread...
Replicating viruses for the treatment of cancer have a number advantages over traditional therapeutic modalities. They are highly targeted, self-amplifying, and added potential to act as both gene-therapy delivery vehicles oncolytic agents. Parapoxvirus ovis or Orf virus (ORFV) is prototypic species genus, causing benign disease in its natural ungulate host. ORFV possesses unique properties that make it an ideal viral backbone development therapeutic: safe humans, has ability cause repeat...
Respiratory syncytial virus infection can cause lower respiratory tract in older adults comparable to influenza, but no vaccines are available.
VA7 is a neurotropic alphavirus vector based on an attenuated strain of Semliki Forest virus. We have previously shown that exhibits oncolytic activity against human melanoma xenografts in immunodeficient mice. The purpose this study was to determine if intravenously administered would be effective glioma.In vitro, U87, U251, and A172 glioma cells were infected killed by VA7-EGFP. In vivo, antiglioma tested Balb/c nude mice using U87 stably expressing firefly luciferase subcutaneous...
In chronic inflammatory reactions such as rheumatoid arthritis and multiple sclerosis, T cells in the inflamed tissue express chemokine receptors CXCR3 CCR5, ligands (CCL) of these are present lesions. However, contribution chemokines to cell recruitment sites inflammation is unclear. addition, relative roles that bind (CXCL9, CXCL10, CXCL11) CCR5 (CCL3, CCL4, CCL5) this process unknown. The vitro chemotaxis vivo migration antigen-activated lymphoblasts unactivated spleen were examined....
In clinical trials, metronomic cyclophosphamide (CPA) is increasingly being combined with vaccines to reduce tumor-induced immune suppression. Previous strategies modulate the system during vaccination have involved continuous administration of low dose chemotherapy, studies that posed unique considerations for trial design. Here, we evaluated CPA in combination a peptide vaccine targeting HPV16E7 an HPV16-induced tumor model, focusing on cytotoxic T-cell response and timing (mCPA) treatment...
Purpose: MRI cell tracking can be used to monitor immune cells involved in the immunotherapy response, providing insight into mechanism of action, temporal progression tumour growth and individual potency therapies. To evaluate whether could track populations response immunotherapy, CD8+ cytotoxic T (CTLs), CD4+CD25+FoxP3+ regulatory (Tregs) myeloid derived suppressor (MDSCs) were labelled with superparamagnetic iron oxide (SPIO) particles. Methods: SPIO-labelled injected mice (one...
Future cancer immunotherapies will combine multiple treatments to generate functional immune responses antigens through synergistic, multi-modal mechanisms. In this study we explored the combination of three distinct immunotherapies: a class I restricted peptide-based vaccine, metronomic cyclophosphamide (mCPA) and anti-PD-1 treatment in murine tumor model expressing HPV16 E7 (C3).
Many pathogens use the same immune evasion mechanisms as cancer cells. Patients with chronic infections have elevated levels of checkpoint receptors (e.g., programed cell death 1, PD1) on T Monoclonal antibody (mAb)-based inhibitors to also been shown enhance T-cell responses in models infection. Therefore, potential act a vaccine "adjuvant" by facilitating expansion antigen-specific repertoires. Here, we report discovery and characterization peptide-based class PD1 inhibitors, which potent...
ABSTRACT The myxoma virus (MV) ankyrin repeat, host range factor M-T5 has the ability to bind and activate cellular Akt, leading permissive MV replication in a variety of diverse human cancer cell lines (G. Wang, J. W. Barrett, M. Stanford, S. Werden, B. Johnston, X. Gao, Sun, Q. Cheng, G. McFadden, Proc. Natl. Acad. Sci. USA 103: 4640-4645, 2006). susceptibility cells infection is directly correlated with basal or induced levels phosphorylated Akt. When deleted from MV, knockout virus,...
Vaccines that can rapidly induce strong and robust antibody-mediated immunity could improve protection from certain infectious diseases for which current vaccine formulations are inefficient. For indications such as anthrax influenza, antibody production in vivo is a correlate of efficacy. Toll-like receptor (TLR) agonists frequently studied their role adjuvants, largely because ability to enhance initiation immune responses antigens by activating dendritic cells. However, TLRs also...