A5017467222- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Virus-based gene therapy research
- Immune Response and Inflammation
- Cancer Research and Treatments
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Animal Virus Infections Studies
- Viral gastroenteritis research and epidemiology
- Adenosine and Purinergic Signaling
- Monoclonal and Polyclonal Antibodies Research
- interferon and immune responses
- Nanoplatforms for cancer theranostics
- Caveolin-1 and cellular processes
- Erythrocyte Function and Pathophysiology
- ATP Synthase and ATPases Research
- Cytokine Signaling Pathways and Interactions
- Veterinary medicine and infectious diseases
- Ovarian cancer diagnosis and treatment
- RNA and protein synthesis mechanisms
- Immune cells in cancer
- Lung Cancer Research Studies
- Mitochondrial Function and Pathology
University of Iowa
2013-2025
University of Iowa Holden Comprehensive Cancer Center
2022
University of Iowa Hospitals and Clinics
2020-2022
Robarts Clinical Trials
2006-2011
Western University
2006-2009
Stomatin-like protein 2 (SLP-2) is a widely expressed mitochondrial inner membrane of unknown function. Here we show that human SLP-2 interacts with prohibitin-1 and -2 binds to the phospholipid cardiolipin. Upregulation expression increases cardiolipin content formation metabolically active membranes induces biogenesis. In T lymphocytes, these events correlate increased complex I II activities, intracellular ATP stores, resistance apoptosis through intrinsic pathway, ultimately enhancing...
The immunologic and therapeutic effects of intratumoral (IT) delivery a novel virus-like particle as lymphoma immunotherapy were evaluated in preclinical studies with human cells murine model. CMP-001 is composed the Qβ bacteriophage capsid protein encapsulating an immunostimulatory CpG-A oligodeoxynucleotide TLR9 agonist. In vitro, induced cytokine production, including IFN-α from plasmacytoid dendritic cells, but only presence anti-Qβ Ab. vivo, IT treatment A20 enhanced survival reduced...
Background CMP-001 is a novel Toll-like receptor-9 agonist that consists of an unmethylated CpG-A motif-rich G10 oligodeoxynucleotide (ODN) encapsulated in virus-like particles. In situ vaccination believed to activate local tumor-associated plasmacytoid dendritic cells (pDCs) leading type I interferon secretion and tumor antigen presentation T systemic antitumor cell responses. This study designed investigate if would enhance head neck squamous carcinoma (HNSCC) response anti-programmed...
Standard cancer therapies, particularly those involving chemotherapy, are in need of modifications that both reduce short-term and long-term side effects as well improve the overall survival patients. Here we show combining low-dose chemotherapy with a therapeutic vaccination using an adenovirus encoding model tumor-associated antigen, ovalbumin (Ad5-OVA), had synergistic impact on tumor-challenged mice. Mice received combinatorial treatment Ad5-OVA plus 5-fluorouracil (5-FU) 95% rate...
Immune checkpoint inhibitors have revolutionized treatment of many types cancer, but are not effective for all patients. One proposed mechanism resistance is lack local interferon production that results in an immunologically “cold” tumor. This barrier may be overcome by direct immune stimulation with TLR9 agonists. Early phase clinical studies a variety cancer demonstrated intratumoral injection agonists, as free drug or formulated into nanoparticles (NP), safe and capable inducing systemic...
Abstract Amid growing evidence that numerous viral infections can produce immunopathology, including nonspecific polyclonal lymphocyte activation, the need to test direct impact of an infecting virus on immune system host is crucial. This best be tested in isolator piglet model which maternal and other extrinsic influences excluded. Therefore, neonatal piglets were colonized with a benign Escherichia coli, or kept germfree, then inoculated wild-type porcine reproductive respiratory syndrome...
Abstract Porcine respiratory and reproductive syndrome virus (PRRSV) causes an extraordinary increase in the proportion of B cells resulting lymphoid hyperplasia, hypergammaglobulinemia, autoimmunity neonatal piglets. Spectratypic analysis from isolator piglets show a non-Gaussian pattern with preferential expansion clones bearing certain H chain third complementary region (HCDR3) lengths. However, only PRRSV-infected was nearly identical spectratype observed for all tissues. This result...
T cell activation through the Ag receptor (TCR) requires sustained signaling from signalosomes within lipid raft microdomains in plasma membrane. In a proteomic analysis of rafts human cells, we identified stomatin-like protein (SLP)-2 as candidate molecule involved receptor. this study, show that SLP-2 expression primary lymphocytes is up-regulated following vivo and ex activation. activated interacts with components TCR polymerized actin. More importantly, up-regulation lines peripheral...
Abstract In situ immunization aims at generating antitumor immune responses through manipulating the tumor microenvironment. On basis of recent advances in understanding immunity, we designed a three-step approach to lymphoma: (i) inducing immunogenic cell death with chemotherapeutic drug doxorubicin. Doxorubicin enhances expression “eat-me” signals by dying cells, facilitating their phagocytosis dendritic cells (DC). Because vesicant activity doxorubicin, microparticles made biodegradable...
Abstract The Toll-like receptor 8 (TLR8) agonist VTX-2337 (motolimod) is an anti-cancer immunotherapeutic agent that believed to augment natural killer (NK) and dendritic cell (DC) activity. goal of this work examine the role TLR8 expression/activity in head neck squamous carcinoma (HNSCC) facilitate prediction responders VTX-2337-based therapy. prognostic expression HNSCC patients was assessed by TCGA tissue microarray analyses. anti-tumor effect determined SCCVII/C3H, mEERL/C57Bl/6...
Adjuvants modulate protective CD8(+) T cell responses generated by cancer vaccines. We have previously shown that immunostimulatory cytosine-phosphodiester-guanine (CpG) oligodeoxynucleotide (ODN) significantly augments tumor protection in mice given adenovirus Here, we examined the impact of chitosan, another candidate vaccine adjuvant, on conferred Unexpectedly, immunization with vaccines combination chitosan provided little against challenge. This directly correlated reduced detection...
Abstract Checkpoint blockade of immune inhibitory pathways is an exciting new approach to inducing durable and clinically relevant anti-tumor responses. Nevertheless, there remains considerable room for improvement despite significant improvements in patient survival following therapy a variety malignancies with monoclonal antibodies that target CTLA4 or the PD-1/PD-L1 pathway. Our goal improve efficacy this cancer by increasing intratumoral release presentation tumor associated antigens....
<h3>Background</h3> One approach to enhancing the anti-tumor T cell response is alter tumor microenvironment (TME) through intratumoral injection (IT) of immunostimulatory agents such as Vidutolimod. Vidutolimod a virus-like particle (VLP) composed TLR9 agonist (CpG-A, known G10) encapsulated by Qβ-bacteriophage capsid. IT shows considerable promise in early phase clinical trials. The immune initiated induction IFNa production pDCs within TME. This effect dependent on coating with antibodies...
Abstract Humanized mouse models can be useful for in vivo preclinical evaluation of mechanisms underlying cancer immunotherapy. Most such involve systemic engraftment immunocompromised mice with human lymphoid and hematopoietic cells, often using normal donor peripheral blood mononuclear cells (PBMCs), followed by inoculation tumor. The ability to control modify immune within the tumor microenvironment (TME), especially NK is limited models. Here, we report development a model designed...