A5042430576- Plant Virus Research Studies
- Bacteriophages and microbial interactions
- Cancer Immunotherapy and Biomarkers
- Histone Deacetylase Inhibitors Research
- Immune cells in cancer
- Transgenic Plants and Applications
- CAR-T cell therapy research
- Virus-based gene therapy research
- HIV/AIDS drug development and treatment
- Photodynamic Therapy Research Studies
- Polymer-Based Agricultural Enhancements
- Click Chemistry and Applications
- Plant Disease Management Techniques
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Nematode management and characterization studies
- Epigenetics and DNA Methylation
- Nanoparticle-Based Drug Delivery
- Protein Degradation and Inhibitors
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer, Stress, Anesthesia, and Immune Response
- Colorectal Cancer Treatments and Studies
- HER2/EGFR in Cancer Research
- Viral gastroenteritis research and epidemiology
- CRISPR and Genetic Engineering
National Cancer Institute
2021-2024
National Institutes of Health
2021-2024
Center for Cancer Research
2021-2024
AstraZeneca (United States)
2024
University of California, San Diego
2018-2024
Cancer Institute (WIA)
2022
Case Western Reserve University
2015-2019
La Jolla Bioengineering Institute
2019
University School
2015-2018
Moores Cancer Center
2018
Collagens in the extracellular matrix (ECM) provide a physical barrier to tumor immune infiltration, while also acting as ligand for inhibitory receptors. Transforming growth factor-β (TGF-β) is key contributor shaping ECM by stimulating production and remodeling of collagens. TGF-β activation signatures collagen-rich environments have both been associated with T cell exclusion lack responses immunotherapy. Here, we describe effect targeting collagens that signal through leukocyte-associated...
Plant parasitic nematodes are a major burden to the global agricultural industry, causing $157 billion loss each year in crop production worldwide. Effective treatment requires large doses of nematicides be applied, putting environment and human health at risk. Challenges treat that located deep within soil, feeding on roots plants. To attack problem its roots, we propose use tobacco mild green mosaic virus (TMGMV), an EPA-approved herbicide as carrier deliver nematicides. TMGMV...
Abstract Poorly inflamed carcinomas do not respond well to immune checkpoint blockade. Converting the tumour microenvironment into a functionally hub would extend clinical benefit of therapy larger proportion cancer patients. Here we show, by using comprehensive single-cell transcriptome, proteome, and cell analysis, that Entinostat, class I histone deacetylase inhibitor, facilitates accumulation necrosis-targeted recombinant murine immune-cytokine, NHS-rmIL12, in experimental mouse colon...
Platform technologies based on plant virus nanoparticles (VNPs) and virus-like particles (VLPs) are attracting the attention of researchers clinicians because biocompatible, biodegradable, noninfectious in mammals, can readily be chemically genetically engineered to carry imaging agents drugs. When Physalis mottle (PhMV) coat protein is expressed Escherichia coli, resulting VLPs nearly identical viruses formed vivo. Here, we isolated PhMV-derived from ClearColi cells carried out external...
Background Immune checkpoint blockade (ICB) has achieved unprecedented success in treating multiple cancer types. However, clinical benefit remains modest for most patients with solid malignancies due to primary or acquired resistance. Tumor-intrinsic loss of major histocompatibility complex class I (MHC-I) and aberrations antigen processing machinery (APM) interferon gamma (IFN-γ) pathways have been shown play an important role ICB While a plethora combination treatments are being...
Molecular imaging approaches and targeted drug delivery hold promise for earlier detection of diseases treatment with higher efficacy while reducing side effects, therefore increasing survival rates quality life. Virus-based nanoparticles are a promising platform because their scaffold can be manipulated both genetically chemically to simultaneously display targeting ligands carrying payloads diagnosis or therapeutic intervention. Here, we displayed 12-amino-acid peptide ligand, GE11...
The solid tumor microenvironment (TME) poses a significant structural and biochemical barrier to immunotherapeutic agents. To address the limitations of penetration distribution enhance antitumor efficacy immunotherapeutics, we present here an autonomous active microneedle (MN) system for direct intratumoral (IT) delivery potent immunoadjuvant, cowpea mosaic virus nanoparticles (CPMV), in vivo. In this system, magnesium (Mg) microparticles embedded into MNs react with interstitial fluid TME,...
Amine/thiol-reactive chemistries are commonly used to conjugate antibodies pharmaceuticals or nanoparticles. Yet, these conjugation strategies often result in unfavorable outcomes such as heterogeneous antibody display with hindered biological activity aggregation due multivalent interactions of the and Here, we report application a site-specific enzymatically driven strategy functionalize virus-based nanoparticles (VNPs). Specifically, an azide-handle was introduced into Fc region set...
Nanoparticle-based technologies, including platforms derived from plant viruses, hold great promise for targeting and delivering cancer therapeutics to solid tumors by overcoming dose-limiting toxicities associated with chemotherapies. A growing body of data indicates advantageous margination penetration properties high aspect-ratio nanoparticles, which enhance payload delivery, resulting in increased efficacy. Our lab has demonstrated that elongated rod-shaped filamentous macromolecular...
Cowpea mosaic virus (CPMV) is currently in the development pipeline for multiple biomedical applications, including cancer immunotherapy.
Fluorous nanoparticles enhances oxygen uptake as a PDT carrier for skin cancers.
Abstract The development of plant viral nanoparticles (VNP) loaded with different molecular versions a photodynamic drug is described. Specifically, tobacco mosaic virus (TMV) and mild green (TMGMV) are developed as carriers that encapsulate the monocationic, dicationic, tricationic, tetracationic porphyrin‐based photosensitizer (Zn‐Por). While TMV has been extensively explored for various nanotechnology applications, this first study investigating TMGMV medical applications. Light‐activated...
The design of versatile tools to improve cell targeting and drug delivery in medicine has become increasingly pertinent nanobiotechnology. Biological inorganic nanocarrier systems are being explored, showing advantages disadvantages terms specificity, internalization, efficient payload delivery, safety profiles. Combining the properties a biological coating on top an nanocarrier, we hypothesize that this hybrid system would nanoparticle–cell interactions, resulting enhanced uptake compared...
Abstract Background: Immune checkpoint blockade (ICB) has limited efficacy in colorectal carcinoma (CRC), where ~85% of patients harbor microsatellite stability (MSS). A minor subset CRC (~15%) instability (MSI) and demonstrate improved responses to ICB ranging from 30-50%. Combination therapy the potential increase response rate. Entinostat, a class I HDAC inhibitor, demonstrated enhance efficacy, such as αPD-1 immunostimulatory cytokines. N-803, heterodimeric IL-15 superagonist that...
Protein cages are promising tools for the controlled delivery of therapeutics and imaging agents when endowed with programmable disassembly strategies. Here, we produced hybrid nanocomposites made tobacco mosaic virus (TMV) magnetic iron oxide nanoparticles (IONPs), designed to disrupt viral protein using magnetically induced release heat. We studied effects this hyperthermia on capsid (1) elongated TMV coated heterogeneously (TMV@IONPs) (2) spherical polystyrene (PS) which deposited...
Immune checkpoint blockade (ICB) targeting the programmed cell death protein 1 (PD-1) and its ligand (PD-L1) fails to provide clinical benefit for most cancer patients due primary or acquired resistance. Drivers of ICB resistance include tumor antigen processing/presentation machinery (APM) IFNγ signaling mutations. Thus, there is an unmet need develop alternative therapies these patients. To this end, we have developed a CRISPR/Cas9 approach generate murine models refractory PD-1/-L1...
Nanoparticle-based pesticide delivery systems have emerged to decrease the environmental and health impact of pesticides while increasing their efficacy. A majority nanopesticides in development pipeline are synthetic materials, some which present own risks. We propose naturally occurring nanomaterials, namely plant viruses such as tobacco mild green mosaic virus (TMGMV), for pesticides. others previously shown that virus-based nanoparticles favorable soil mobility properties thus could...
Abstract There is strong evidence that chemotherapy can induce tumor necrosis which be exploited for the targeted delivery of immuno-oncology agents into microenvironment (TME). We hypothesized docetaxel, a chemotherapeutic agent induces necrosis, in combination with bifunctional molecule NHS-IL-12 (M9241), delivers recombinant IL-12 through specific targeting necrotic regions tumor, would provide significant antitumor benefit poorly inflamed murine model, EMT6 (breast), and moderately...
<h3>Background</h3> Rilvegostomig is a monovalent, bispecific humanized IgG1 monoclonal antibody that binds to human TIGIT and PD-1 with high affinity. has shown promising antitumor activity in adult patients phase I/II clinical trial (NCT04995523) currently being investigated two Phase III trials (NCT06109779, NCT06357533). Here, we report vitro/in vivo/ex vivo pharmacodynamic effects of rilvegostomig its murine surrogate preclinical cancer models. <h3>Methods</h3> In vitro, CD8-mediated...
<h3>Background</h3> Combination of antibody drug conjugates (ADC) and immunotherapy (IO) is emerging as a treatment paradigm with clinical efficacy in several tumor indications. Identifying translatable pre-clinical models to demonstrate the potential novel ADC IO combinations has been challenge for field. We describe development humanized mouse model NSCLC which demonstrates significant anti-tumor activity microenvironment (TME) regulation response combination checkpoint immunotherapy....
<h3>Background</h3> Immune checkpoint blockade (ICB) has achieved unprecedented success in treating multiple cancer types. However, clinical benefit remains modest for most patients with solid malignancies the majority having primary resistance to these therapies. Additionally, many that initially respond often acquire resistance. Tumor-intrinsic loss of MHC class I and aberrations interferon gamma (IFNγ) pathway have been shown play an important role ICB Entinostat, a HDAC inhibitor,...
Adeno-associated virus (AAV) has emerged as a promising gene delivery vector because of its non-pathogenicity, simple structure and genome, low immunogenicity compared to other viral vectors. However, wide adoption safe effective therapy treatment for disease may rely on targeting the deliver transgenes desired cell populations. To this end, our group developed protease-activatable (PAV) based AAV that responds elevated protease activity commonly found in many diseased tissue...