- CAR-T cell therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Glioma Diagnosis and Treatment
- Immune cells in cancer
- Nanowire Synthesis and Applications
- Immunotherapy and Immune Responses
- Extracellular vesicles in disease
- interferon and immune responses
- Biosimilars and Bioanalytical Methods
- Clusterin in disease pathology
- Advancements in Semiconductor Devices and Circuit Design
- S100 Proteins and Annexins
- Studies on Chitinases and Chitosanases
- Biomedical Ethics and Regulation
- Cancer Research and Treatments
Jacksonville College
2024
WinnMed
2022-2024
Mayo Clinic in Florida
2022-2024
University of North Florida
2023-2024
INTRODUCTION: Glioblastoma Multiforme (GBM), the most common and devastating primary brain cancer, resists standard of care. Gene therapy, anti-angiogenics, immune checkpoint inhibitors (ICI) struggle to gain FDA approval have failed against GBM. Adoptive T-cell immunotherapy; Chimeric Antigen Receptor (CAR) therapy has shown safety efficacy in recent clinical trials. Success is still impeded by tumor heterogeneity, antigen loss immunosuppressive microenvironment (TME). METHODS: Our CAR...
Immunosuppression within the tumor microenvironment (TME) poses a significant challenge to efficacy of Chimeric Antigen Receptor (CAR) T-cell therapy in solid tumors, including glioblastoma (GBM), most common and deadly primary brain tumor. Tumor TME-residing immunosuppressive cells can hijack program death 1(PD1) pathway evade antitumor immunity by upregulating its ligand, PD-L1. Thus, targeting PD-L1 emerges as promising therapeutic strategy simultaneously eliminate components TME. We...
Glioblastoma (GBM) is the most prevalent and aggressive malignant primary brain tumor. GBM proximal to lateral ventricles (LVs) more aggressive, potentially because of subventricular zone contact. Despite this, cross-talk between neural stem/progenitor cells (NSC/NPCs) not well understood. Using cell-specific proteomics, we show that LV-proximal prevents neuronal maturation NSCs through induction senescence. In addition, tumor-initiating (BTICs) increase expression cathepsin B (CTSB) upon...
Chimeric antigen receptor (CAR) T cell therapy has encountered limited success in solid tumors. The lack of dependable antigens and the immunosuppressive tumor microenvironment (TME) are major challenges. Within TME, cells along with employ an immune-evasion mechanism that upregulates programmed death ligand 1 (PD-L1) to deactivate effector cells; this makes PD-L1 a reliable, universal target for We developed novel CAR (MC9999) using our humanized anti-PD-L1 monoclonal antibody, designed...
Abstract Chimeric antigen receptor (CAR) T-cell therapy has encountered limited success in solid tumors. The lack of dependable antigens and the immunosuppressive tumor microenvironment (TME) are major challenges. Within TME, cells along with employ an immune-evasion mechanism that upregulates programmed death ligand 1 (PD-L1) to deactivate effector T cells; this makes PD-L1 a reliable, universal target for We developed novel CAR (MC9999) using our humanized anti-PD-L1 monoclonal antibody,...
With the goal to overcome limited treatment options and poor prognosis of glioblastoma (GBM), we have developed a PD-L1-targeting CAR T cell therapy, MC9999. In vitro experiments with MC9999 cells derived from GBM patients exhibited potent, antigen-specific cytotoxicity against autologous tumor immunosuppressive within microenvironment (TME). an orthotopic model using patient-derived brain tumor-initiating cells, intracranial delivery eradicated established tumors improved survival....
Glioblastoma (GBM) is the most prevalent and aggressive malignant primary brain tumor. GBM proximal to lateral ventricles (LVs) more aggressive, potentially due subventricular zone (SVZ) contact. Despite this, crosstalk between neural stem/progenitor cells (NSC/NPCs) not well understood. Using cell-specific proteomics, we show that LV-proximal prevents neuronal maturation of NSCs through induction senescence. Additionally, tumor initiating (BTICs) increase expression CTSB upon interaction...
Abstract Glioblastoma (GBM) is the most common and aggressive primary neoplasm of central nervous system. The location GBM contributes significantly to patient outcomes, where tumors contacting lateral ventricles (LVs) have increased expression stem cell genes, incidence distal recurrence, decreased overall survival. While reasons for these findings are not fully understood, we hypothesize they arise due interactions with subventricular zone (SVZ), largest neurogenic niche in mammals. We...
Abstract Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. GBM tumors proximal to lateral ventricles have a worse prognosis with multifocality, recurrence, lower overall survival. Studies suggest this increased aggressiveness attributed cerebrospinal fluid (CSF), as we previously observed transcriptomic changes cells upon CSF exposure. GlioVis database reveals chitinase 3-like protein 1 (CHI3L1), glycoprotein secreted by immune cancer cells, associated poor...