Carley Fowler
A5038604308- CAR-T cell therapy research
- Adenosine and Purinergic Signaling
- Cytomegalovirus and herpesvirus research
- Nanowire Synthesis and Applications
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Glioma Diagnosis and Treatment
- Immune Cell Function and Interaction
- Extracellular vesicles in disease
- T-cell and B-cell Immunology
- Nanoplatforms for cancer theranostics
- Viral Infectious Diseases and Gene Expression in Insects
- Immunotherapy and Immune Responses
Stanford University
2023-2024
Adenosine (Ado) mediates immune suppression in the tumor microenvironment and exhausted CD8+ CAR-T cells express CD39 CD73, which mediate proximal steps Ado generation. Here, we sought to enhance cell potency by knocking out CD39, or adenosine receptor 2a (A2aR) but observed only modest effects. In contrast, overexpression of deaminase (ADA-OE), metabolizes inosine (INO), induced stemness enhanced functionality. Similarly, exposure INO augmented function features stemness. profound metabolic...
H3K27M-mutant diffuse midline gliomas (DMGs) express high levels of the disialoganglioside GD2 (ref. 1). Chimeric antigen receptor-modified T cells targeting (GD2-CART) eradicated DMGs in preclinical models2. Arm A Phase I trial no. NCT04196413 3) administered one intravenous (IV) dose autologous GD2-CART to patients with pontine (DIPG) or spinal DMG (sDMG) at two (DL1, 1 × 106 kg−1; DL2, 3 kg−1) following lymphodepleting chemotherapy. Patients clinical imaging benefit were eligible for...
Abstract The intensive nutrient requirements needed to sustain T cell activation and proliferation, combined with competition for nutrients within the tumor microenvironment, raise prospect that glucose availability may limit CAR-T function. Here, we seek test hypothesis stable overexpression (OE) of transporter GLUT1 in primary human cells would improve their function antitumor potency. We observe GLUT1OE increases consumption, glycolysis, glycolytic reserve, oxidative phosphorylation,...
Abstract Background Chimeric Antigen Receptor (CAR) T cells are now standard of care (SOC) for some patients with B cell and plasma malignancies could disrupt the therapeutic landscape solid tumors. However, access to CAR-T is not adequate meet clinical needs, in part due high cost long lead times manufacturing grade virus. Non-viral site directed CAR integration can be accomplished using CRISPR/Cas9 double-stranded DNA (dsDNA) or single-stranded (ssDNA) via homology-directed repair (HDR),...
H3K27M-mutant diffuse midline gliomas (DMGs) express high levels of the GD2 disialoganglioside and chimeric antigen receptor modified T-cells targeting (GD2-CART) eradicate DMGs in preclinical models. Arm A Phase I trial NCT04196413 administered one IV dose autologous GD2-CART to patients with pontine (DIPG) or spinal (sDMG) glioma at two (DL1=1e6/kg; DL2=3e6/kg) following lymphodepleting (LD) chemotherapy. Patients clinical imaging benefit were eligible for subsequent...
Adenosine (Ado) mediates immune suppression in the tumor microenvironment and exhausted CD8
Abstract BACKGROUND H3K27M-mutant diffuse midline gliomas (DMGs) express uniformly high levels of the GD2 disialoganglioside. In preclinical models, chimeric antigen receptor modified T-cells (CAR T-cells) targeting robustly regressed orthotopically xenografted DMGs. METHODS This Phase I trial (NCT04196413) administered one IV dose autologous transduced with a GD2-CAR retroviral vector to patients pontine (DIPG) or spinal (sDMG) at two (DL1=1e6 T-cells/kg; DL2=3e6 T-cells/kg) following...
Abstract Chimeric antigen receptors (CARs) are synthetic that link an extracellular tumor specific domain to intracellular signaling domains. Despite of remarkable results against refractory B cell malignancies, intense effort is underway augment the potency CAR T cells in order overcome suppressive microenvironment, which associated with exhaustion. Adenosine a major mediator immune suppression. Ectoenzyme CD39 plays central role generation adenosine by catalyzing metabolism ATP into...
<h3>Background</h3> CAR T cells have been highly effective against refractory B cell malignancies but not demonstrated sustained antitumor effects solid tumors. Intense effort is underway to augment the potency of in order overcome suppressive tumor microenvironment, which associated with exhaustion. Adenosine a major mediator immune suppression. CD39 (ecto-ATP diphosphohydrolase-1) plays central role generation adenosine by catalyzing metabolism ATP into ADP/AMP. CD73 (59-ectonucleotidase)...