Zachary Ehlinger
A5091691424- CAR-T cell therapy research
- Glioma Diagnosis and Treatment
- Viral Infectious Diseases and Gene Expression in Insects
- Lymphoma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Chronic Myeloid Leukemia Treatments
- Silicon Carbide Semiconductor Technologies
- Hematopoietic Stem Cell Transplantation
- Acute Lymphoblastic Leukemia research
- Advancements in Semiconductor Devices and Circuit Design
- Acute Myeloid Leukemia Research
- Immune cells in cancer
- Extracellular vesicles in disease
- Virus-based gene therapy research
- Integrated Circuits and Semiconductor Failure Analysis
- Phagocytosis and Immune Regulation
- Multiple Myeloma Research and Treatments
- Radiopharmaceutical Chemistry and Applications
- CRISPR and Genetic Engineering
- Immunodeficiency and Autoimmune Disorders
- Cancer Immunotherapy and Biomarkers
- Neuroinflammation and Neurodegeneration Mechanisms
- Single-cell and spatial transcriptomics
- Neutropenia and Cancer Infections
Stanford Cancer Institute
2021-2025
Cancer Prevention Institute of California
2024-2025
Stanford University
2020-2024
Stratford University
2024
Palo Alto University
2021-2023
Abstract Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas (DMGs) are universally lethal paediatric tumours of the central nervous system 1 . We have previously shown that disialoganglioside GD2 is highly expressed on cells demonstrated promising preclinical efficacy GD2-directed chimeric antigen receptor (CAR) T 2 , providing rationale for a first-in-human phase I clinical trial (NCT04196413). Because CAR cell-induced brainstem inflammation can result...
Abstract Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Ten 16 large B cell lymphoma (LBCL) disease after CAR19 treatment had absent or low CD19. Lower surface CD19 density pretreatment was associated To prevent relapse − lo disease, we tested a bispecific CAR targeting and/or CD22 (CD19-22.BB.z-CAR) in phase I clinical trial ( NCT03233854 ) adults relapsed/refractory acute...
Abstract Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed large B-cell lymphoma (LBCL). We evaluated long-term course hematologic recovery, immune reconstitution, and infectious complications 41 patients with LBCL treated axicabtagene ciloleucel (axi-cel) at a single center. Grade 3+ cytopenias occurred 97.6% within first 28 days postinfusion, most resolved by 6 months. Overall, 63.4% received red...
Abstract Adoptively transferred T cells and agents designed to block the CD47–SIRPα axis are promising cancer therapeutics that activate distinct arms of immune system 1,2 . Here we administered anti-CD47 antibodies in combination with adoptively goal enhancing antitumour efficacy but observed abrogated therapeutic benefit due rapid macrophage-mediated clearance expressing chimeric antigen receptors (CARs) or engineered cell receptors. Anti-CD47-antibody-mediated CAR was potent enough serve...
Abstract Chimeric antigen receptor (CAR) T cells directed against CD19 (CAR19) are a revolutionary treatment for B-cell lymphomas (BCLs). CAR19 cell expansion is necessary function but also associated with toxicity. To define the impact of on patient outcomes, we prospectively followed cohort 236 patients treated (brexucabtagene autoleucel or axicabtagene ciloleucel) mantle lymphoma (MCL), follicular lymphoma, and large BCL (LBCL) over course 5 years obtained data using peripheral blood...
BackgroundOutcomes are poor for patients with large B-cell lymphoma who relapse after CD19-directed chimeric antigen receptor (CAR) T-cell therapy (CAR19). CD22 is a nearly universally expressed surface and the efficacy of CD22-directed CAR (CAR22) in unknown, which was what we aimed to examine this study.MethodsIn single centre, open-label, dose-escalation phase 1 trial, intravenously administered CAR22 at two dose levels (1 million 3 CAR22-positive T cells per kg bodyweight) adult (aged...
Abstract Patients with large B-cell lymphoma (LBCL) progressing after anti-CD19 CAR T-cell (CAR19) therapy have poor outcomes. Subsequent shows promise, but the impact of residual CAR19 and early relapse remains unclear. We evaluated 37 CAR19-refractory LBCL patients who received anti-CD22 (CAR22) in a phase 1b trial (NCT04088890). Residual was unquantifiable 17 33 evaluable post-CAR22 infusion. Single-cell RNA sequencing revealed minimal CAR19/CAR22 co-transduction. Peak transgene levels...
<div>Abstract<p>Patients with large B-cell lymphoma that progresses after anti–CD19 chimeric antigen receptor (CAR) T-cell (CAR19) therapy have poor outcomes. Subsequent CAR shows promise, but the impact of residual CAR19 and early relapse remains unclear. We evaluated 37 patients CAR19-refractory who received anti–CD22 (CAR22) in a phase Ib trial (NCT04088890). Residual was unquantifiable 17 33 evaluable post-CAR22 infusion. Single-cell RNA sequencing revealed minimal...
<p>CAR T-cell surveillance methods and time points of the two cohorts</p>
<p>Linear regression analysis of CAR22 transduction efficiency, vector copy number (VCN) and T cell subsets in CD4/CD8 enrichment material product (A) Linear efficiency versus material. (B) the products. (C) VCN (D) products.</p>
<p>Cytopenia within 28 days following CAR22 infusion in early and late groups. (A) The nadir white blood cell count, hemoglobin levela platelet count were comparable between (B) Similar administration of filgrastim given dosage, red transfusion burden groups.</p>
<p>Maximal expansion (CMax) and area under the curve from day 0 to 28 (AUC0-28) of CAR22 post-infusion, as assessed by flow cytometry (A) qPCR (B), in early late groups patients</p>
<p>Comparative analysis of Comparative T cell subsets CD4/CD8 enrichment material during CAR22 manufacturing process. (A) CD4+ and (B) CD8+ cells.</p>
<p>Comparative analysis of CAR22 transduction rate, vector copy number (VCN) and T cell subset in products between patients who experienced disease progression (PD) within 90 days versus more than after CAR19 therapy (A) Patients PD post-CAR19 infusion exhibited lower rates VCN their compared to those days. (B) The was similar the 2 groups.</p>
<p>Comparison of CAR19 transgene level, CAR22 product characteristic and cell kinetics across different co-stimulatory domain</p>
<p>Sensitivity analysis for handling residual CAR19 qPCR data below limit of quantification (LOQ) in leukapheresis material</p>
<p>CD39 expression on CD4+ and CD8+ CAR22, stratified by median levels (High/Low) or using a 20% cutoff, its correlation with CAR22 expansion as measured flow cytometry qPCR, treatment response, survival outcomes. (A) The CD39 level in the product, (> < median) shows no significant difference maximal (CMax) peripheral blood (PB) after infusion. (B) median, area under curve from day 0 to 28 (AUC0-28) post-infusion PB. (C) CMax AUC0-28 qPCR (D) complete response rate,...
<p>CAR22 product release criteria</p>
<p>CAR22 construction</p>
<p>The CAR T-cell maximal expansion (CMax) and area under the curve from day 0 to 28 (AUC0-28) for CAR19 CAR22 following or infusion in same patient. (A) Analysis by flow cytometry. (B) qPCR assay. No statistical comparison was performed due limited number of patients.</p>
<p>Quantifiable CAR19 transgene levels in leukapheresis material and CAR22 products, their correlation with complete response (CR) rate survival outcomes. (A) The CR is similar between patients without quantifiable products. (B) Progression-free (PFS) overall (OS) are material. (C) PFS OS products.</p>
<p>Cohort 2: Patient demographics upon receiving CAR19 or CAR22 therapies</p>