A5010868067- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Glioma Diagnosis and Treatment
- Viral Infectious Diseases and Gene Expression in Insects
- Nanowire Synthesis and Applications
- Cancer Immunotherapy and Biomarkers
- Virus-based gene therapy research
- Advancements in Semiconductor Devices and Circuit Design
- Biomedical Ethics and Regulation
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Biosimilars and Bioanalytical Methods
- Silicon Carbide Semiconductor Technologies
- Cytomegalovirus and herpesvirus research
- CRISPR and Genetic Engineering
- 3D Printing in Biomedical Research
- T-cell and B-cell Immunology
- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
- Cancer Cells and Metastasis
- Radiomics and Machine Learning in Medical Imaging
- Neuroinflammation and Neurodegeneration Mechanisms
- Pelvic and Acetabular Injuries
Beckman Research Institute
2016-2025
City of Hope
2016-2025
City Of Hope National Medical Center
2016-2025
CTI BioPharma (United Kingdom)
2016-2023
University of Massachusetts Amherst
2022
Data Harbor (United States)
2015
Roger Williams Medical Center
2014
Providence College
2014
Boston University
2014
University of Birmingham
2012
A patient with recurrent multifocal glioblastoma received chimeric antigen receptor (CAR)-engineered T cells targeting the tumor-associated interleukin-13 alpha 2 (IL13Rα2). Multiple infusions of CAR were administered over 220 days through two intracranial delivery routes - into resected tumor cavity followed by ventricular system. Intracranial IL13Rα2-targeted not associated any toxic effects grade 3 or higher. After T-cell treatment, regression all and spinal tumors was observed, along...
Abstract Purpose: A first-in-human pilot safety and feasibility trial evaluating chimeric antigen receptor (CAR)–engineered, autologous primary human CD8+ cytotoxic T lymphocytes (CTL) targeting IL13Rα2 for the treatment of recurrent glioblastoma (GBM). Experimental Design: Three patients with GBM were treated IL13(E13Y)-zetakine CTL IL13Rα2. Patients received up to 12 local infusions at a maximum dose 108 CAR-engineered cells via catheter/reservoir system. Results: We demonstrate...
Abstract The interleukin (IL) 13 receptor α2 (IL13Rα2) is a glioma-restricted cell-surface epitope not otherwise detected within the central nervous system. Here, we describe novel approach for targeting glioblastoma multiforme (GBM) with IL13Rα2-specific cytolytic T cells (CTLs) by their genetic modification to express membrane-tethered IL13 cytokine chimeric T-cell antigen receptor, or zetakine. Our prototype zetakine incorporates an E13Y mutein selective binding IL13Rα2. Human...
Improvements in the quality and fitness of chimeric antigen receptor (CAR)-engineered T cells, through CAR design or manufacturing optimizations, could enhance therapeutic potential CAR-T cells. One parameter influencing effectiveness cell therapy is differentiation status final product: cells that are less-differentiated less exhausted more therapeutically effective. In current study, we demonstrate expanded IL15 (CAR-T/IL15) preserve a stem memory (Tscm) phenotype, defined by expression...
PET gene reporter imaging can be used to monitor the trafficking of therapeutic cytotoxic T cells in glioma patients.
Purpose: Metastasis to the brain from breast cancer remains a significant clinical challenge, and may be targeted with CAR-based immunotherapy. CAR design optimization for solid tumors is crucial due absence of truly restricted antigen expression potential safety concerns "on-target off-tumor" activity. Here, we have optimized HER2-CAR T cells treatment metastases, determined optimal second-generation route administration xenograft mouse models metastatic tumors, including multifocal...
T cell immunotherapy is emerging as a powerful strategy to treat cancer and may improve outcomes for patients with glioblastoma (GBM). We have developed chimeric antigen receptor (CAR) targeting IL-13 α2 (IL13Rα2) the treatment of GBM. Here, we describe optimization IL13Rα2-targeted CAR cells, including design 4-1BB (CD137) co-stimulatory (IL13BBζ) manufacturing platform using enriched central memory cells. Utilizing orthotopic human GBM models patient-derived tumor sphere lines in NSG mice,...
High-grade gliomas are extremely difficult to treat because they invasive and therefore not curable by surgical resection; the toxicity of current chemo- radiation therapies limits doses that can be used. Neural stem cells (NSCs) have inherent tumor-tropic properties enable their use as delivery vehicles target enzyme/prodrug therapy selectively tumors. We used a cytosine deaminase (CD)-expressing clonal human NSC line, HB1.F3.CD, home in mice locally convert prodrug 5-fluorocytosine active...
To evaluate IL13Rα2 as an immunotherapeutic target for eliminating glioma stem-like cancer initiating cells (GSC) of high-grade gliomas, with particular focus on the potential genetically engineered IL13Rα2-specific primary human CD8(+) CTLs (IL13-zetakine(+) CTL) to this therapeutically resistant subpopulation.A panel low-passage GSC tumor sphere (TS) and serum-differentiated lines were expanded from patient glioblastoma specimens. These evaluated expression susceptibility IL13-zetakine(+)...
Abstract Purpose: The majority of tumor-specific antigens are intracellular and/or secreted and therefore inaccessible by conventional chimeric antigen receptor (CAR) T-cell therapy. Given that all intracellular/secreted proteins processed into peptides presented class I MHC on the surface tumor cells, we used alpha-fetoprotein (AFP), a specific liver cancer marker, as an example to determine whether peptide–MHC complexes can be targets for CAR therapy against solid tumors. Experimental...
Chimeric antigen receptor–modified (CAR-modified) T cells have shown promising therapeutic effects for hematological malignancies, yet limited and inconsistent efficacy against solid tumors. The refinement of CAR therapy requires an understanding the optimal characteristics cellular products, including appropriate composition CD4+ CD8+ subsets. Here, we investigated differential antitumor effect targeting glioblastoma-associated (GBM-associated) IL-13 receptor α2 (IL13Rα2). Upon stimulation...
CAR T cells using chlorotoxin as the tumor-targeting domain recognize and kill glioblastoma with high specificity potency.
Abstract Chimeric antigen receptor (CAR)-T cell therapy has shown remarkable clinical efficacy against B-cell malignancies, yet marked vulnerability to escape and tumor relapse exists. Here we report the rational design optimization of bispecific CAR-T cells with robust activity heterogeneous multiple myeloma (MM) that is resistant conventional targeting maturation (BCMA). We demonstrate BCMA/CS1 exhibit superior CAR expression function compared T co-express individual BCMA CS1 CARs....
Abstract Chimeric antigen receptor (CAR) T cells mediate potent antigen-specific antitumor activity; however, their indirect effects on the endogenous immune system are not well characterized. Remarkably, we demonstrate that CAR T-cell treatment of mouse syngeneic glioblastoma (GBM) activates intratumoral myeloid and induces memory responses coupled with feed-forward propagation responses. IFNγ production by responsiveness host critical for tumor landscape remodeling to promote a more...
Chimeric antigen receptor T cell (CAR-T) therapy is an emerging strategy to improve treatment outcomes for recurrent high-grade glioma, a cancer that responds poorly current therapies. Here we report completed phase I trial evaluating IL-13Rα2-targeted CAR-T cells in 65 patients with the majority being glioblastoma (rGBM). Primary objectives were safety and feasibility, maximum tolerated dose/maximum feasible dose recommended 2 plan. Secondary included overall survival, disease response,...
Abstract Background Wide-spread application of chimeric antigen receptor (CAR) T cell therapy for cancer is limited by the current use autologous CAR cells necessitating manufacture individualized therapeutic products each patient. To address this challenge, we have generated an off-the-shelf, allogeneic product treatment glioblastoma (GBM), and present here feasibility, safety, potential approach. Methods We clinical a healthy-donor derived IL13Rα2-targeted CAR+ (IL13-zetakine+) cytolytic...
Promoter-specific recruitment of histone acetyltransferase activity is often critical for transcriptional activation. We present a detailed study the interaction between complexes SAGA and NuA4, transcription activators. demonstrate by affinity chromatography photo–cross-linking label transfer that acidic activators directly interact with Tra1p, shared subunit NuA4. Mutations within COOH-terminus Tra1p disrupted its resulted in gene-specific defects correlated lowered promoter-specific...
The prevalence of lumbosacral intervertebral disk bulge and herniation on sagittal magnetic resonance (MR) images was determined in 45 pregnant subjects 41 asymptomatic nonpregnant women childbearing age. MR technique differed for the groups. Fifty-three percent 54% had an abnormal (bulge or herniation) at one more levels (L3-4, L4-5, L5-S1). difference not statistically significant. There also no significant distribution outcomes among subjects, 17 parous women, 24 nulliparous women....