A5021784997- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Antimicrobial Peptides and Activities
- Lung Cancer Research Studies
- Virus-based gene therapy research
- vaccines and immunoinformatics approaches
- TGF-β signaling in diseases
- Cancer Research and Treatments
- Advanced biosensing and bioanalysis techniques
- Viral Infections and Outbreaks Research
- Radiation Dose and Imaging
- Protein Kinase Regulation and GTPase Signaling
- Cancer Treatment and Pharmacology
- Cancer therapeutics and mechanisms
- Supramolecular Self-Assembly in Materials
- Fibroblast Growth Factor Research
- Advanced Drug Delivery Systems
- Immune cells in cancer
- Cancer-related molecular mechanisms research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Peptidase Inhibition and Analysis
- Pneumonia and Respiratory Infections
- Epigenetics and DNA Methylation
Melanoma Institute Australia
2022
Rutgers, The State University of New Jersey
2017-2019
Rutgers Cancer Institute of New Jersey
2017-2019
The University of Texas Medical Branch at Galveston
2013-2018
The University of Texas MD Anderson Cancer Center
2018
Galveston College
2015
John Sealy Hospital
2015
Significance Immunotherapy has revolutionized cancer treatment, yielding unprecedented long-term responses and survival. However, a significant proportion of patients remain refractory, which correlates with the absence immune-infiltrated (“hot”) tumors. Here, we observed that FDA-approved unadjuvanted seasonal influenza vaccines administered via intratumoral injection not only provide protection against active virus lung infection, but also reduce tumor growth by increasing antitumor CD8 +...
ONC201 is a first-in-class, orally active antitumor agent that upregulates cytotoxic TRAIL pathway signaling in cancer cells. has demonstrated safety and preliminary efficacy first-in-human trial which patients were dosed every 3 weeks. We hypothesized dose intensification of may impact efficacy. discovered exerts dose- schedule-dependent effects on tumor progression cell death vivo. With intensification, we note potent anti-metastasis effect inhibition migration invasion. Our preclinical...
<h3>Background</h3> ONC201 is a small molecule antagonist of DRD2, G protein-coupled receptor overexpressed in several malignancies, that has prolonged antitumor efficacy and immunomodulatory properties preclinical models. The first-in-human trial previously established recommended phase II dose (RP2D) 625 mg once every three weeks. Here, we report the results I study evaluated safety, pharmacokinetics (PK), pharmacodynamics (PD) weekly ONC201. <h3>Methods</h3> Patients ≥ 18 years old...
The inability of CD8+ effector T cells (Teffs) to reach tumor is an important aspect resistance cancer immunotherapy. recruitment these the microenvironment (TME) regulated by integrins, a family adhesion molecules that are expressed on cells. Here, we show 7HP349, small-molecule activator lymphocyte function-associated antigen-1 (LFA-1) and very late activation antigen-4 (VLA-4) integrin cell-adhesion receptors, facilitated preferential localization tumor-specific improved antitumor...
Chikungunya virus (CHIKV) is an arthritogenic alphavirus that during the last decade has significantly expanded its geographical range and caused large outbreaks of human disease around world. Although mortality rates associated with CHIKV are low, acute chronic illnesses by represent a significant burden largely affecting low middle income countries. This report summarizes current status vaccine development for CHIKV.
d-Amino acid analogs of peptides and proteins are attractive for applications in biotechnology medicine due to their reduced proteolytic sensitivity. Here, we report that self-assembling peptide nanofibers composed d-amino acids act as immune adjuvants, investigate ability induce antibody responses comparison l-amino counterparts. The model antigenic OVA (chicken egg ovalbumin aa 323–339) from chicken ovalbumin, known elicit mice, was linked an l- or domain generate enantiomeric displaying...
Recent data shows that fibroblast growth factor 14 (FGF14) binds to and controls the function of voltage-gated sodium (Nav) channel with phenotypic outcomes on neuronal excitability. Mutations in FGF14 gene humans have been associated brain disorders are partially recapitulated Fgf14–/– mice. Thus, signaling pathways modulate FGF14:Nav interaction may be important therapeutic targets. Bioluminescence-based screening small molecule modulators FGF14:Nav1.6 complex identified...
To combat mucosal pathogens that cause gastrointestinal (GI) infections, local immunity is required which best achieved through oral vaccination.
Bacillus Calmette-Guerin (BCG) is the only vaccine against TB and has limited protection efficacy, which wanes past adolescence. Multifunctional CD8+ T cells (IFN-γ+/TNF-α+/IL-2+) are associated with lower reactivation risk enhanced control of active Mtb infection. Since boosting BCG contraindicated, booster vaccines that augment cell immunity in lungs BCG-vaccinated individuals urgently needed. We developed a vaccination strategy based on self-assembling peptide nanofibers presenting...
Natural and synthetic biomaterials are increasingly being used for the development of vaccines immunotherapies as alternatives to traditional live-attenuated formulations due their improved safety profiles no risk reversion virulence. Polymeric materials in particular enjoy attention ease fabrication, control over physicochemical properties, wide range immunogenicity. While majority studies focus on inducing protective antibody responses, recent years, materials-based strategies delivery...
Abstract ONC201, a first-in-class oral anti-tumor agent, upregulates the pro-apoptotic immune cytokine TRAIL and activates integrated stress response leading to upregulation of death receptor 5 in bulk tumor cancer stem cells. We previously demonstrated that ONC201 exerts dose- schedule-dependent effect on progression vivo while suppressing Akt/ERK signaling tumors dose/frequency-dependent manner (Wagner et al., AACR, 2016). also provided evidence exhibits potent anti-metastatic observe...
2586 Background: ONC201 is an orally active, small molecule selective antagonist of the G protein-coupled receptor DRD2 that has established a new class compounds referred to as imipridones. A first-in-human trial defined its recommended phase II dose (RP2D) 625mg using once every three week administration was very well tolerated at doses yielded antitumor effects. also showed stimulatory effects on immune cells in preclinical studies, including increased intratumoral NK cell infiltration...
Abstract We recently reported that acute concomitant infection in a tissue distant from the tumor results trafficking of tumor-specific CD8+ T cells microenvironment to site and accelerated growth host death. However, we hypothesized anti-viral responses within (rather than it), possibly even without productive viral replication, can reprogram local lead long-term regression. Indeed, discovered mouse model melanoma (B16-F10), injection live influenza (A/H1N1/PR8), heat-inactivated influenza,...
Abstract Purpose: Studies have shown that bone morphogenetic protein (BMP) signaling is aberrantly expressed in lung and other carcinoma leading to pro-oncogenic effects on tumor growth. The BMP receptor inhibitor DMH2 induces death of cancer cells through the downregulation anti-apoptotic proteins XIAP, TAK1, Id1-Id3. Since does not downregulate vivo because metabolic instability poor pharmacokinetics better inhibitors are needed. Experimental Design: Here, we identified a site designed...
Abstract In recent years, immunotherapy has yielded increased survival for cancer patients; however, a significant percentage of patient tumors remain refractory to immunotherapy. This is due in part the absence an inflamed tumor microenvironment. our effort utilize anti-pathogen vaccination recruit immune cells un-infiltrated (cold) tumors, we observed that intratumoral injection influenza A/PR8/H1N1 lysate (but not live virus) reduced B16-F10 melanoma growth (p&lt;0.01). Towards...