A5084741818- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Viral Infectious Diseases and Gene Expression in Insects
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- Nanowire Synthesis and Applications
- CRISPR and Genetic Engineering
- Silicon Carbide Semiconductor Technologies
- Advancements in Semiconductor Devices and Circuit Design
- Kruppel-like factors research
- RNA Interference and Gene Delivery
- Cancer Immunotherapy and Biomarkers
- Neuroblastoma Research and Treatments
- Hematopoietic Stem Cell Transplantation
- Immunodeficiency and Autoimmune Disorders
- Chronic Myeloid Leukemia Treatments
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related gene regulation
- Cytomegalovirus and herpesvirus research
- Radiation Effects in Electronics
- Electrostatic Discharge in Electronics
- Transgenic Plants and Applications
- Biosimilars and Bioanalytical Methods
- 3D Printing in Biomedical Research
Texas Children's Hospital
2016-2025
Baylor College of Medicine
2016-2025
Houston Methodist
2016-2025
Methodist Hospital
2016-2025
Children's Cancer Center
2025
Baylor University Medical Center
2018-2023
Baylor University
2018-2023
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...
Antigen-independent tonic signaling by chimeric antigen receptors (CARs) can increase differentiation and exhaustion of T cells, limiting their potency. Incorporating 4-1BB costimulation in CARs may enable cells to resist this functional exhaustion; however, the potential ramifications CAR remain unclear. Here, we found that CAR-derived produce toxicity via continuous TRAF2-dependent activation nuclear factor κB (NF-κB) pathway augmented FAS-dependent cell death. This mechanism was amplified...
Abstract Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death in world, and curative systemic therapies are lacking. Chimeric antigen receptor (CAR)–expressing T cells induce robust antitumor responses patients with hematologic malignancies but have limited efficacy solid tumors, including HCC. IL15 IL21 promote T-cell expansion, survival, function can improve properties cells. We explored whether transgenic expression and/or enhanced glypican-3-CAR...
The successful immunotherapy of acute myeloid leukemia (AML) has been hampered because most potential antigenic targets are shared with normal hematopoietic stem cells (HSCs), increasing the risk sustained and severe toxicity following treatment. C-type lectin-like molecule 1 (CLL-1) is a membrane glycoprotein expressed by >80% AML but absent on HSCs. Here we describe development evaluation CLL-1-specific chimeric antigen receptor T (CLL-1.CAR-Ts) demonstrate their specific activity against...
Chimeric antigen receptor (CAR) T cell therapy for the treatment of acute myeloid leukemia (AML) has risk toxicity to normal cells. CD7 is expressed by leukemic blasts and malignant progenitor cells approximately 30% AML patients but absent on erythroid Since expression also linked with chemoresistance poor outcomes, targeting this may be beneficial subset patients. Here, we show that a CD7-directed CAR in gene-edited (CD7KO) effectively eliminates CD7+ lines, primary AML, colony-forming...
T cells expressing second-generation chimeric antigen receptors (CARs) specific for CD5, a T-cell surface marker present on normal and malignant cells, can selectively kill tumor cells. We aimed to improve this killing by substituting the CD28 costimulatory endodomain (28.z) with 4-1BB (BB.z), as 28.z CD5 CAR rapidly differentiated into short-lived effector In contrast, costimulation is known promote development of central memory subpopulation. Here, we found BB.z had impaired growth...
Chimeric antigen receptor (CAR) T-cell therapy targeting acute lymphoblastic leukemia (T-ALL) faces limitations such as selection and limited persistence. CD7 is an attractive for T-ALL, but overlapping expression on healthy T cells leads to fratricide of CD7-CAR cells, requiring additional genetic modification. We took advantage naturally occurring CD7- generate (CD7-CARCD7-) cells. CD7-CARCD7- exhibited a predominantly CD4+ memory phenotype had significant antitumor activity upon chronic...
Chimeric antigen receptor (CAR)-mediated targeting of T lineage antigens for the therapy blood malignancies is frequently complicated by self-targeting CAR cells or their excessive differentiation driven constant signaling. Expression CARs CD7, a pan-T cell highly expressed in and some myeloid leukemias, produces robust fratricide often requires additional mitigation strategies, such as CD7 gene editing. In this study, we show can be fully prevented using ibrutinib dasatinib, pharmacologic...
Chimeric antigen receptor T cells (CART) targeting CD19 through CD28.ζ signaling induce rapid lysis of leukemic blasts, contrasting with persistent tumor control exhibited by 4-1BB.ζ-CART. We reasoned that molecular dynamics at the CART immune synapse (CARIS) could explain differences in their rejection kinetics. observed CD28.ζ-CART engaged brief highly lethal CARIS and mastered serial killing, whereas 4-1BB.ζ-CART formed lengthy relied on robust expansion cooperative killing. analyzed...
Subsequent malignancies are well-documented complications in long-term follow-up of cancer patients. Recently, genetically modified immune effector (IE) cells have shown benefit hematologic and being evaluated clinical trials for solid tumors. Although the short-term IE well described, there is limited literature summarizing follow-up, including subsequent malignancies. We retrospectively reviewed data from 340 patients treated across 27 investigator-initiated pediatric adult at our center....
Background C-type lectin-like molecule 1 (CLL-1) is highly expressed in acute myeloid leukemia (AML) but absent primitive hematopoietic progenitors, making it an attractive target for a chimeric antigen receptor (CAR) T-cell therapy. Here, we optimized our CLL-1 CAR anti-leukemic activity mouse xenograft models of aggressive AML. Methods First, the using different spacer, transmembrane and costimulatory sequences. We used second retroviral vector to coexpress transgenic IL15. measured...
Abstract The outcome of therapy with chimeric Ag receptor (CAR)-modified T cells is strongly influenced by the subset origin infused cells. However, because polyclonally activated acquire a largely CD45RO+CCR7− effector memory phenotype after expansion, regardless origin, it impossible to know which subsets contribute final cell product. To determine contribution naive cell, stem central and terminally differentiated populations CD3 CD28–activated CAR-modified that we use for therapy,...
Human cytomegalovirus (HCMV) reactivations are associated with lower overall survival after transplantations. Adoptive transfer of HCMV-reactive expanded or selected T cells can be applied as a compassionate use, but requires that the human leukocyte antigen-matched donor provides memory against HCMV. To overcome this, we developed engineered expressing chimeric antigen receptors (CARs) targeted HCMV glycoprotein B (gB) expressed upon viral reactivation. Single-chain variable fragments...