A5030044268- CAR-T cell therapy research
- Acute Lymphoblastic Leukemia research
- Hematopoietic Stem Cell Transplantation
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Acute Myeloid Leukemia Research
- Viral Infectious Diseases and Gene Expression in Insects
- Immunodeficiency and Autoimmune Disorders
- Childhood Cancer Survivors' Quality of Life
- Advancements in Semiconductor Devices and Circuit Design
- Blood disorders and treatments
- Chronic Lymphocytic Leukemia Research
- Neuroblastoma Research and Treatments
- Nanowire Synthesis and Applications
- CRISPR and Genetic Engineering
- Biosimilars and Bioanalytical Methods
- Chronic Myeloid Leukemia Treatments
- Integrated Circuits and Semiconductor Failure Analysis
- Lymphoma Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Biomedical Ethics and Regulation
- Autoimmune and Inflammatory Disorders Research
- Mesenchymal stem cell research
- Cancer Immunotherapy and Biomarkers
- Palliative Care and End-of-Life Issues
National Cancer Institute
2016-2025
National Institutes of Health
2016-2025
Center for Cancer Research
2016-2025
Lasker Foundation
2025
Cancer Institute (WIA)
2018-2024
University of Michigan
2024
Scleroderma Foundation
2024
National Cancer Institute
2013-2024
Medical College of Wisconsin
2023
Diabetes Australia
2022
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...
PURPOSE Patients with B-cell acute lymphoblastic leukemia who experience relapse after or are resistant to CD19-targeted immunotherapies have limited treatment options. Targeting CD22, an alternative antigen, represents alternate strategy. We report outcomes on the largest patient cohort treated CD22 chimeric antigen receptor (CAR) T cells. PATIENTS AND METHODS conducted a single-center, phase I, 3 + dose-escalation trial large expansion that tested CD22-targeted CAR cells for children and...
CD19 chimeric antigen receptor (CD19-CAR) T cells induce high response rates in children and young adults (CAYAs) with B-cell acute lymphoblastic leukemia (B-ALL), but relapse are high. The role for allogeneic hematopoietic stem-cell transplant (alloHSCT) following CD19-CAR T-cell therapy to improve long-term outcomes CAYAs has not been examined.We conducted a phase I trial of autologous CD19.28ζ-CAR relapsed or refractory B-ALL. Response clinical were assessed relation disease treatment...
Despite high remission rates following CAR-T cell therapy in B-ALL, relapse due to loss of the targeted antigen is increasingly recognized as a mechanism immune escape. We hypothesized that simultaneous targeting CD19 and CD22 may reduce likelihood loss, thus improving sustained rates. A systematic approach generation CAR constructs incorporating two target-binding domains led several novel CD19/CD22 bivalent constructs. Importantly, we demonstrate challenges associated with construction...
Although inotuzumab ozogamicin (InO) is recognized as an effective agent in relapsed acute lymphoblastic leukemia (ALL) adults, data on safety and efficacy pediatric patients are scarce. We report the use of InO 51 children with relapsed/refractory ALL treated compassionate program. In this heavily pretreated cohort, complete remission was achieved 67% overt marrow disease. The majority (71%) responders were negative for minimal residual Responses observed irrespective cytogenetic subtype or...
T cell-mediated hyperinflammatory responses, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS), are now well-established toxicities of chimeric antigen receptor (CAR) cell therapy. As the field CAR cells advances, however, there is increasing recognition that hemophagocytic lymphohistiocytosis (HLH)-like following infusion occurring broadly across patient populations constructs. Importantly, these HLH-like often not directly associated with CRS...
Relapse following chimeric antigen receptor (CAR) T-cell therapy directed against CD19 for relapsed/refractory B-acute lymphoblastic leukemia (r/r B-ALL) remains a significant challenge. Three main patterns of relapse predominate: positive (CD19pos) relapse, negative (CD19neg) and lineage switch (LS). Development validation risk factors that predict phenotype could help define potential pre- or post-CAR infusion interventions aimed at decreasing relapse. Our group sought to extensively...
The clinical use of chimeric antigen receptor (CAR) T-cell therapy is growing rapidly due to expanding indications for standard care treatment and the development new investigational products. establishment consensus diagnostic criteria cytokine release syndrome (CRS) immune effector cell associated neurotoxicity (ICANS), alongside steady both tocilizumab corticosteroids treatment, have been essential facilitating widespread use. Pre-emptive interventions prevent more severe toxicities has...
Children's Oncology Group trial AALL1621 was conducted to prospectively determine the safety and efficacy of inotuzumab ozogamicin (InO) in pediatric adolescent patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL).
Abstract The T cell receptor fusion construct (TRuC) gavocabtagene autoleucel (gavo-cel) consists of single-domain anti-mesothelin antibody that integrates into the endogenous (TCR) and engages signaling capacity entire TCR upon mesothelin binding. Here we describe phase 1 results from an ongoing phase1/2 trial gavo-cel in patients with treatment-refractory mesothelin-expressing solid tumors. primary objectives were to evaluate safety determine recommended 2 dose (RP2D). Secondary included...
Background CD22 is a B‐lineage differentiation antigen that has emerged as leading therapeutic target in acute lymphoblastic leukemia (ALL). Procedure Properties of expression relevant to targeting were characterized primary samples obtained from children and young adults with relapsed chemotherapy refractory B‐precursor (pre‐B) ALL. Results was demonstrated all subjects (n = 163) detection on at least 90% blasts 155 cases. Median site density surface 3,470 sites/cell (range 349–19,653, n...
Abstract Purpose: Chimeric antigen receptor T-cell (CART) therapy targeting CD22 induces remission in 70% of patients with relapsed/refractory acute lymphoblastic leukemia (ALL). However, the majority post-CD22 CART remissions are short and associated reduction expression. We evaluate implications low density on activity propose mechanisms to overcome escape. Experimental Design: Using ALL cell lines variable expression, we cytokine profile, cytotoxicity, vivo functionality setting develop a...