A5052695746- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- CAR-T cell therapy research
- Infant Nutrition and Health
- RNA Interference and Gene Delivery
- Cancer Research and Treatments
- Cancer Immunotherapy and Biomarkers
- Immune Response and Inflammation
- Neonatal Respiratory Health Research
- Adenosine and Purinergic Signaling
- Bacteriophages and microbial interactions
- Neuroblastoma Research and Treatments
- Toxin Mechanisms and Immunotoxins
- Cytokine Signaling Pathways and Interactions
- Immune cells in cancer
- Glycosylation and Glycoproteins Research
- interferon and immune responses
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Clinical Nutrition and Gastroenterology
- T-cell and Retrovirus Studies
- HIV Research and Treatment
- Veterinary Oncology Research
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
Organogenesis (United States)
2022-2025
ImmunoGen (United States)
2022-2025
The University of Texas at El Paso
2012-2020
Targeted Medical Pharma (United States)
2013
University of Turin
1991-2008
Agennix (United States)
2004-2008
University of Illinois Chicago
2006
Baylor College of Medicine
2006
University of Illinois Urbana-Champaign
2006
University of Pennsylvania
2004
Abstract Following an infection or immunization, a primary CD8+ T cell response generally rises then falls rapidly before giving rise to “memory” response. When we immunized mice with recombinant viral immunogens optimized enhance the lytic capability of cells, measured profound depression in Ag-specific effector function after early restimulation. Indeed, “mirror image” cytolytic was observed: most powerful immunogens, as by capacity 6 days elicited weakest secondary immune when evaluated...
Abstract The transforming rat Her-2/neu oncogene embedded into the genome of virgin transgenic BALB/c mice (BALB-neuT) provokes development an invasive carcinoma in each their 10 mammary glands. i.m. vaccination with DNA plasmids coding for extracellular and transmembrane domains protein product started when already display multifocal situ carcinomas temporarily halts neoplastic progression, but all develop a tumor by week 43. By contrast, progressive clearance lesions complete protection...
Lactoferrin (LF) is an important protein component of the innate immune system that broadly distributed within body fluids. LF endowed with multiple biological activities. Talactoferrin (TLF), a recombinant human LF, in clinical development as anticancer agent and entering Phase III trials. Here, we show TLF induces maturation dendritic cells (DCs) derived from monocytes. TLF, at physiologically relevant concentrations (100 microg/ml) up-regulates expression leukocyte antigen (HLA) class II,...
Abstract A retroviral infection was used to introduce the cDNA coding for mouse IL-4 into parental cells of a spontaneous adenocarcinoma BALB/c mice (TS/A-pc). Four clones releasing between 5 40 U (10(5) cells) in 48 h culture were selected. The secretion does not affect their vitro growth, whereas ability form tumor vivo inversely correlates with amount secreted. Although morphologic observation suggested that rejection clone D5.40 (releasing IL-4) depends on eosinophil cytolysis,...
Abstract In this work, we investigated the anticancer activity of orally administered recombinant human lactoferrin (rhLF) alone and in combination with chemotherapy tumor‐bearing mice. rhLF inhibited growth squamous cell carcinoma (O12) tumors T cell–immunocompromised nu/nu mice by 80% when at 1,000 mg/kg (2.9 g/m 2 ) oral gavage twice daily for 8 days ( p < 0.001). Similar was observed syngeneic, immunocompetent BALB/c mice, where (1,000 mg/kg, 2.9 once daily) halted mammary...
Abstract Evidence is presented that interleukin (IL)‐2 maintains viability of human polymorphonuclear cells (PMN) in culture by preventing these from undergoing programmed cell death (PCD) and induces the synthesis new RNA protein. Our laboratory has recently discovered PMN constitutively express IL‐2β receptor more importantly, are able to respond functionally IL‐2 enhanced growth inhibitory activity against an opportunistic fungal pathogen, Candida albicans. We now report was interfere...
Abstract Janus kinase 3 (JAK3) is a cytoplasmic tyrosine required for T cell development and activated by cytokines that utilize the interleukin-2 (IL-2) receptor common gamma chain (γc). Genetic inactivation of JAK3 manifested as severe combined immunodeficiency disease (SCID) in humans mice. These findings have suggested represents pharmacological target to control certain lymphoid-derived diseases. Here we provide novel evidence AG-490 potently inhibits autokinase activity phosphorylation...
Systemic gene delivery using cationic liposome–DNA complexes (LDCs) has been shown to elicit potent antitumor activity in mice with tumor metastases the lungs. However, intravenous for treatment of established cancer not evaluated previously a spontaneous, large animal model. We therefore safety, toxicity, and efficacy delivery, LDCs dogs metastases. Twenty chemotherapy-resistant osteosarcoma lungs received series infusions liposomes plasmid DNA encoding canine interleukin-2 (IL-2) cDNA....
Aggressive forms of breast cancer, such as Her2+ and triple negative cancer (TNBC), are enriched in stem cells (BCSC) have limited therapeutic options. BCSC represent a key cellular reservoir for relapse, metastatic progression resistance. Their ability to resist common cytotoxic therapies relies on different mechanisms, including improved detoxification. The cystine-glutamate antiporter protein xCT (SLC7A11) regulates cystine intake, conversion cysteine subsequent glutathione synthesis,...
Background: The activation of stimulator interferon genes (STING) has emerged as a promising strategy to reprogram the tumor microenvironment (TME) and enhance antitumor immunity. We previously demonstrated that combining potent STING agonist (8803, IMGS-203) with novel dual-specific anti-PD-L1/PD-L2 monoclonal antibody (27907) produced curative responses in checkpoint-refractory models. In this study, we investigated mechanisms underlying these effects by analyzing TME tumors treated...
Abstract Introduction: Antibody blockade of either the Programmed Death 1 (PD-1) immune checkpoint receptor on T cells or its cognate ligand PD-L1 tumor and stroma has revolutionized oncology but fails to regress “cold” tumors lacking cell infiltration. We leveraged iterative selection capacity yeast-displayed fully human antibody identify dual PD-L1/PD-L2 specific antibodies (DIPDL) that block their engagement both PD-1 B7-1. Finally, we engineered these DIPDL efficiently kill PD-L2...
Metastatic breast cancer (MBC) is the leading cause of death in women due to recurrence and resistance conventional therapies. Thus, MBC represents an important unmet clinical need for new treatments. In this paper we generated a virus-like particle (VLP)-based vaccine (AX09) inhibit de novo metastasis formation ultimately prolong survival patients with MBC. To aim, engineered bacteriophage MS2 VLP display extracellular loop xCT, promising therapeutic target involved tumor progression...
Lactoferrin, a key component of innate immunity, is cationic monomeric 80-kDa glycoprotein the transferrin superfamily. Recombinant human lactoferrin, known as talactoferrin (TLF), induces distinct functional maturation program in dendritic cells (DCs) derived from peripheral blood monocytes. However, receptors and molecular mechanisms involved this induction have not been fully determined. By exploiting genome-wide transcription profiling immature DCs, TNF-α- IL-1β-matured DCs (m-DCs),...
Impaired immune responses are frequently observed in tumor-bearing hosts during progression of tumor growth, but the molecular basis these functional defects remains unclear. To investigate tumor-induced immunosuppression, we first established that lymphocytes from mice bearing s.c. mammary adenocarcinoma (TS/A) tumors were severely impaired their ability to generate cellular and humoral Ag-specific responses. Lymphocytes then screened for abnormalities expression signal transducing proteins...
Abstract HIV-1 infection is accompanied by qualitative and quantitative defects in CD4+ T lymphocytes. Loss of immune function HIV patients usually associated with a profound dysregulation cytokine production. To investigate whether signaling occur during infection, PHA blasts from healthy human donors were infected two strains screened for the expression STAT proteins used signaling. A selective decrease STAT5B was seen 8 days after BZ167 dual-tropic isolate, but not Ba-L, M-tropic strain....
Administration of plasmid/lipid complexes to the lung airways for treatment metastatic pulmonary diseases represents a new strategy gene therapy. In this study we present evidence that intratracheal administration plasmid encoding murine IL-12 complexed with N-[1-(2,3-dioleyloxy)propyl)- N,N,N-trimethylammonium chloride:cholesterol inhibits growth metastases, using renal cell carcinoma model. Instillation pIL-12/lipid resulted in expression biologically active (170-240 pg/ml) and IFN-gamma...
A plasmid expression system encoding murine IFN-alpha4 and complexed with a protective interactive noncondensing polymeric (PINC) delivery was used for in vivo immunotherapy treatment of an immunogenic renal cell carcinoma, Renca, nonimmunogenic mammary adenocarcinoma, TS/A. Mice bearing established tumors were treated IFN-alpha/polyvinylpyrrolidone (PVP) complexes via direct intratumoral injection. Up to 100% inhibition tumor growth observed the mice. By using optimal dose 96 48 microg...