A5029941019- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Cancer Immunotherapy and Biomarkers
- Hematopoietic Stem Cell Transplantation
- Immune Cell Function and Interaction
- Acute Lymphoblastic Leukemia research
- Monoclonal and Polyclonal Antibodies Research
- Glioma Diagnosis and Treatment
- Nanowire Synthesis and Applications
- Immunodeficiency and Autoimmune Disorders
- Cytomegalovirus and herpesvirus research
- Viral Infectious Diseases and Gene Expression in Insects
- Biosimilars and Bioanalytical Methods
- Polyomavirus and related diseases
- Blood disorders and treatments
- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
- Neuroblastoma Research and Treatments
- Advancements in Semiconductor Devices and Circuit Design
- T-cell and B-cell Immunology
- CRISPR and Genetic Engineering
- Mast cells and histamine
- Cancer Research and Treatments
- Viral-associated cancers and disorders
Texas Children's Hospital
2016-2025
Baylor College of Medicine
2016-2025
Houston Methodist
2015-2025
Methodist Hospital
2015-2025
Children's Cancer Center
2012-2025
RWTH Aachen University
2024
Dan L Duncan Comprehensive Cancer Center
2024
Icahn School of Medicine at Mount Sinai
2024
Universitätsklinikum Aachen
2022
Oxfam
2022
Purpose The outcome for patients with metastatic or recurrent sarcoma remains poor. Adoptive therapy tumor-directed T cells is an attractive therapeutic option but has never been evaluated in sarcoma. Patients and Methods We conducted a phase I/II clinical study which recurrent/refractory human epidermal growth factor receptor 2 (HER2) –positive received escalating doses (1 × 10 4 /m to 1 8 ) of expressing HER2-specific chimeric antigen CD28.ζ signaling domain (HER2-CAR cells). Results...
<h3>Importance</h3> Glioblastoma is an incurable tumor, and the therapeutic options for patients are limited. <h3>Objective</h3> To determine whether systemic administration of HER2-specific chimeric antigen receptor (CAR)–modified virus-specific T cells (VSTs) safe these have antiglioblastoma activity. <h3>Design, Setting, Participants</h3> In this open-label phase 1 dose-escalation study conducted at Baylor College Medicine, Houston Methodist Hospital, Texas Children’s with progressive...
In preclinical models of glioblastoma, antigen escape variants can lead to tumor recurrence after treatment with CAR T cells that are redirected single antigens. Given the heterogeneous expression antigens on glioblastomas, we hypothesized a bispecific molecule would mitigate and improve antitumor activity cells. Here, created joins HER2-binding scFv an IL13Rα2-binding IL-13 mutein make tandem exodomain (TanCAR) CD28.ζ endodomain. We determined patient TanCAR showed distinct binding HER2 or...
Targeted T cells are emerging as effective non-toxic therapies for cancer. Multiple elements, however, contribute to the overall pathogenesis of cancer through both distinct and redundant mechanisms. Hence, targeting multiple cancer-specific markers simultaneously could result in better therapeutic efficacy. We created a functional chimeric antigen receptor-the TanCAR, novel artificial molecule that mediates bispecific activation cells. demonstrate feasibility cumulative integration...
Glioblastoma (GBM) is the most common primary malignant brain cancer, and currently incurable. Chimeric antigen receptor (CAR) T cells have shown promise in GBM treatment. While we that combinatorial targeting of 2 glioma antigens offsets escape enhances T-cell effector functions, interpatient variability surface expression between patients hinders clinical impact pairs. This study addresses 3 using a single CAR product for broader application.
Abstract Purpose: Glioblastoma multiforme (GBM) is the most aggressive human primary brain tumor and currently incurable. Immunotherapies have potential to target GBM stem cells, which are resistant conventional therapies. Human epidermal growth factor receptor 2 (HER2) a validated immunotherapy target, we determined if HER2-specific T cells can be generated from patients that will autologous HER2-positive GBMs their CD133-positive cell compartment. Experimental Design: 10 consecutive were...
Preclinical and early clinical studies have demonstrated that chimeric antigen receptor (CAR)-redirected T cells are highly promising in cancer therapy. We observed targeting HER2 a glioblastoma (GBM) cell line results the emergence of HER2-null tumor maintain expression nontargeted tumor-associated antigens. Combinational these antigens could therefore offset this escape mechanism. studied single-cell coexpression patterns HER2, IL-13Rα2, EphA2 primary GBM samples using multicolor flow...
Outcomes for patients with glioblastoma (GBM) remain poor despite aggressive multimodal therapy. Immunotherapy genetically modified T cells expressing chimeric antigen receptors (CARs) targeting interleukin (IL)-13Rα2, epidermal growth factor receptor variant III (EGFRvIII), or human 2 (HER2) has shown promise the treatment of gliomas in preclinical models and a clinical study (IL-13Rα2). However, IL-13Rα2 EGFRvIII is associated development loss variants, there are safety concerns HER2....
Abstract Chimeric antigen receptor (CAR) T-cells targeting CD19 demonstrate remarkable efficacy in treating B-lineage acute lymphoblastic leukemia (BL-ALL), yet up to 39% of treated patients relapse with CD19(−) disease. We report that escape is associated downregulation, but preservation, targetable expression CD20 and CD22. Accordingly, we reasoned broadening the spectrum CD19CAR include both CD22 would enable them target BL-ALL while preserving their upfront efficacy. created a...
Human epidermal growth factor receptor 2 (HER2) is expressed by the majority of human osteosarcomas and a risk for poor outcome. Unlike breast cancer, osteosarcoma cells express HER2 at too low, level patients to benefit from monoclonal antibodies. We reasoned that this limitation might be overcome genetically modifying T with HER2-specific chimeric antigen receptors (CARs), because even low frequency engagement could sufficient induce effector cell killing tumor. were generated retroviral...
Abstract Medulloblastoma is a common malignant brain tumor of childhood. Human epidermal growth factor receptor 2 (HER2) expressed by 40% medulloblastomas and risk for poor outcome with current aggressive multimodal therapy. In contrast to breast cancer, HER2 only at low levels in medulloblastomas, rendering monoclonal antibodies ineffective. We determined if T cells grafted HER2-specific chimeric antigen (CAR; cells) recognized killed HER2-positive medulloblastomas. Ex vivo, stimulation...
Abstract Triple-negative breast cancer (TNBC) is an aggressive disease lacking targeted therapy. In this study, we developed a CAR T cell–based immunotherapeutic strategy to target TEM8, marker initially defined on endothelial cells in colon tumors that was discovered recently be upregulated TNBC. were upon specific recognition of TEM8 secreted immunostimulatory cytokines and killed tumor as well TEM8-positive TNBC cells. Notably, the stem–like cells, offsetting formation mammospheres...
Abstract Refractory metastatic rhabdomyosarcoma is largely incurable. Here we analyze the response of a child with refractory bone marrow to autologous HER2 CAR T cells. Three cycles cells given after lymphodepleting chemotherapy induces remission which consolidated four more T-cell infusions without lymphodepletion. Longitudinal immune-monitoring reveals remodeling receptor repertoire immunodominant clones and serum autoantibodies reactive oncogenic signaling pathway proteins. The disease...
Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) can be modified to function as heterologous tumor directed effector cells that survive longer in vivo than without specificity, due chronic stimulation by viral antigens expressed during persistent infection seropositive individuals. We evaluated the nonviral piggyBac (PB) transposon system a platform for modifying EBV-CTLs express functional human epidermal growth factor receptor 2-specific chimeric antigen (HER2-CAR) thereby...
Central nervous system Langerhans cell histiocytosis (CNS-LCH) brain involvement may include mass lesions and/or a neurodegenerative disease (LCH-ND) of unknown etiology. The goal this study was to define the mechanisms pathogenesis that drive CNS-LCH.Cerebrospinal fluid (CSF) biomarkers including CSF proteins and extracellular BRAFV600E DNA were analyzed in from patients with CNS-LCH compared tumors other conditions. Additionally, presence tested peripheral mononuclear blood cells (PBMCs)...
We identify a population of Protogenin-positive (PRTG