A5079756020- CAR-T cell therapy research
- Nanowire Synthesis and Applications
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Glioma Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
Seattle Children's Hospital
2023-2024
University of Pennsylvania
2020-2022
Antigen heterogeneity that results in tumor antigenic escape is one of the major obstacles to successful chimeric antigen receptor (CAR) T cell therapies solid tumors including glioblastoma multiforme (GBM). To address this issue and improve efficacy CAR therapy for GBM, we developed an approach combines cells with inhibitor apoptosis protein (IAP) antagonists, a new class small molecules mediate degradation IAPs, treat GBM. Here, demonstrated IAP antagonist birinapant could sensitize GBM...
<title>Abstract</title> Diffuse intrinsic pontine glioma (DIPG) is a fatal brainstem tumor desperately in need of better treatments. CAR T cell therapies for DIPG have demonstrated clinical tolerability and bioactivity, but not universal benefit. A major obstacle insufficient trafficking to the tumor. As our trials locoregional elevation CXCL10, ligand chemokine receptor CXCR3, we aimed leverage this CXCL10 enhance by engineering B7-H3-targeting cells overexpress CXCR3 variants. Here,...
B7-H3 CAR T cell treatment in combination with ONC206 aims to assess benefit and significant extension of survival orthotopic DIPG mouse models. BACKGROUND. Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric tumor arising the pons affecting over 300 children each year United States. Chimeric antigen receptor (CAR) cells, targeted immunotherapy showing remarkable results treating hematologic cancers, have recently been translated DIPG. protein expressed nearly all but present at...
Prior to adoptive transfer, CAR T cells are activated, lentivirally infected with transgenes, and expanded over 9 11 days. An unintended consequence of this process is the progressive differentiation time in culture. Differentiated engraft poorly, which limits their ability persist provide sustained tumor control hematologic as well solid tumors. Solid tumors include other barriers cell therapies, including immune metabolic checkpoints that suppress effector function durability. Sialic acids...
Abstract Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric tumor of the pons affecting over 300 children in U.S. each year. Chimeric antigen receptor (CAR) T cells are targeted immunotherapy with remarkable clinical success against hematological malignancies and now being investigated central nervous system (CNS) tumors. B7-H3 surface specifically expressed on nearly all DIPG but not normal brain providing an attractive therapeutic window. Therefore, Seattle Children’s opened...
Abstract BACKGROUND Diffuse midline glioma (DMG), including diffuse intrinsic pontine (DIPG), remains a fatal disease. We have published the preclinical efficacy of HER2, EGFR806, and B7-H3 CAR-T cells opened 3 trials (BrainChild-01, -02, -03, respectively) that delivered &gt;350 intracranial CAR T doses to &gt;70 enrolled children with recurrent/refractory CNS tumors DIPG/DMG. While these demonstrated feasibility tolerability repeated, locoregional cell dosing, responses not been...