A5087281332- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Virus-based gene therapy research
- Hematopoietic Stem Cell Transplantation
- Cancer Immunotherapy and Biomarkers
- Viral Infectious Diseases and Gene Expression in Insects
- Chronic Lymphocytic Leukemia Research
- Nanowire Synthesis and Applications
- Herpesvirus Infections and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Biosimilars and Bioanalytical Methods
- HIV Research and Treatment
- Multiple Myeloma Research and Treatments
- Advancements in Semiconductor Devices and Circuit Design
- Silicon Carbide Semiconductor Technologies
- Lymphoma Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- Immunodeficiency and Autoimmune Disorders
- Biomedical Ethics and Regulation
- Neuroblastoma Research and Treatments
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
University of Washington
2016-2025
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2009-2024
Fred Hutch Cancer Center
2015-2024
University of Washington Medical Center
2016-2024
Cancer Research Center
2008-2023
Lyell Immunopharma (United States)
2021-2023
Clinical Research Management
2014-2021
GTx (United States)
2020
Weatherford College
2020
Technical University of Munich
2011-2017
T cells that have been modified to express a CD19-specific chimeric antigen receptor (CAR) antitumor activity in B cell malignancies; however, identification of the factors determine toxicity and efficacy these has challenging prior studies which phenotypically heterogeneous CAR-T products were prepared from unselected cells.We conducted clinical trial evaluate CD19 manufactured defined CD4+ CD8+ subsets administered CD4+:CD8+ composition adults with acute lymphoblastic leukemia after...
Cytomegalovirus (CMV) disease in immunocompromised patients correlates with a deficiency of CD8+ cytotoxic T lymphocytes specific for CMV. We evaluated the safety and immunologic effects immunotherapy clones these recipients allogeneic bone marrow transplants.
The adoptive transfer of antigen-specific T cells to establish immunity is an effective therapy for viral infections and tumors in animal models. application this approach human disease would require the isolation vitro expansion evidence that such persist function vivo after transfer. Cytomegalovirus-specific CD8 + cytotoxic cell (CTL) clones could be isolated from bone marrow donors, propagated vitro, adoptively transferred immunodeficient transplant recipients. No toxicity developed...
Adoptive T cell therapy, involving the ex vivo selection and expansion of antigen-specific clones, provides a means augmenting immunity without in constraints that can accompany vaccine-based strategies. A phase I study was performed to evaluate safety, persistence, efficacy adoptively transferred CD8 + clones targeting tumor-associated antigens, MART1/MelanA gp100 for treatment patients with metastatic melanoma. Four infusions autologous were administered, first IL-2 subsequent low-dose (at...
Lymphodepletion chemotherapy followed by infusion of CD19-targeted chimeric antigen receptor-modified T (CAR-T) cells can be complicated neurologic adverse events (AE) in patients with refractory B-cell malignancies. In 133 adults treated CD19 CAR-T cells, we found that acute lymphoblastic leukemia, high CD19+ bone marrow, cell dose, cytokine release syndrome, and preexisting comorbidities were associated increased risk AEs. Patients severe neurotoxicity demonstrated evidence endothelial...
CD19-specific chimeric antigen receptor (CAR)-modified T cells have antitumor activity in B cell malignancies, but factors that affect toxicity and efficacy been difficult to define because of differences lymphodepletion heterogeneity CAR-T administered individual patients. We conducted a clinical trial which CD19 were manufactured from defined subsets 1:1 CD4(+)/CD8(+) ratio 32 adults with relapsed and/or refractory non-Hodgkin's lymphoma after cyclophosphamide (Cy)-based chemotherapy or...
The adoptive transfer of antigen-specific T cells that have been expanded ex vivo is being actively pursued to treat infections and malignancy in humans. cell populations are available for immunotherapy include both effector memory central cells, these differ phenotype, function, homing. efficacy requires transferred persist vivo, but identifying can reproducibly survive after they numerically by vitro culture has proven difficult. Here we show macaques, CD8+ clones derived from not...
Purpose We evaluated the safety and feasibility of anti-CD19 chimeric antigen receptor-modified T (CAR-T) cell therapy in patients with chronic lymphocytic leukemia (CLL) who had previously received ibrutinib. Methods Twenty-four CLL lymphodepleting chemotherapy CAR-T cells at one three dose levels (2 × 105, 2 106, or 107 cells/kg). Nineteen experienced disease progression while receiving ibrutinib, were ibrutinib intolerant, two did not experience Six venetoclax refractory, 23 a complex...
Newly assembled major histocompatibility complex (MHC) class I molecules, together with the endoplasmic reticulum chaperone calreticulin, interact transporter associated antigen processing (TAP) through a molecule called tapasin. The molecular cloning of tapasin revealed it to be transmembrane glycoprotein encoded by an MHC-linked gene. It is member immunoglobulin superfamily probable cytoplasmic retention signal. Up four MHC I–tapasin complexes were found bind each TAP molecule. Expression...
The adoptive transfer of T cells modified to express a chimeric antigen receptor (CAR) comprised an extracellular single-chain antibody (scFV) fragment specific for tumor cell surface molecule, and linked intracellular signaling module, has activity in advanced malignancies. tyrosine kinase-like orphan 1 (ROR1) is tumor-associated molecule expressed prevalent B-lymphoid epithelial cancers absent on normal mature B vital tissues, making it candidate CAR T-cell therapy.We constructed ROR1-CARs...
Abstract The use of synthetic chimeric antigen receptors (CAR) to redirect T cells recognize tumor provides a powerful new approach cancer immunotherapy; however, the attributes CARs that ensure optimal in vivo recognition remain be defined. Here, we analyze influence length and composition IgG-derived extracellular spacer domains on function CARs. Our studies demonstrate CD19-CARs with long from IgG4 hinge-CH2-CH3 are functional vitro but lack antitumor activity due interaction between Fc...