A5087021014- CAR-T cell therapy research
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Acute Lymphoblastic Leukemia research
- Immune Cell Function and Interaction
- Silicon Carbide Semiconductor Technologies
- Integrated Circuits and Semiconductor Failure Analysis
- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Acute Myeloid Leukemia Research
- Hematopoietic Stem Cell Transplantation
- Advancements in Semiconductor Devices and Circuit Design
- Nanowire Synthesis and Applications
- Immunotherapy and Immune Responses
- Lymphoma Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Glioma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Advanced biosensing and bioanalysis techniques
- Cancer therapeutics and mechanisms
- Neuroblastoma Research and Treatments
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- DNA Repair Mechanisms
Sheba Medical Center
2014-2025
Tel Aviv University
2014-2025
Edmond and Lily Safra Children's Hospital
2013-2025
Israel Medical Association
2024
Arthur M. Sackler Gallery
2022
Cancer Research Center
2019
Moffitt Cancer Center
2019
National Cancer Institute
1998-2017
National Institutes of Health
2014-2017
Center for Cancer Research
2015-2017
The CD19 antigen, expressed on most B-cell acute lymphoblastic leukemias (B-ALL), can be targeted with chimeric antigen receptor-armed T cells (CART-19), but relapses epitope loss occur in 10% to 20% of pediatric responders. We detected hemizygous deletions spanning the locus and de novo frameshift missense mutations exon 2 some relapse samples. However, we also discovered alternatively spliced mRNA species, including one lacking 2. Pull-down/siRNA experiments identified SRSF3 as a splicing...
Abstract Adoptive immunotherapy using chimeric antigen receptor (CAR) expressing T cells targeting the CD19 B lineage has demonstrated marked success in relapsed pre-B-cell acute lymphoblastic leukaemia (ALL). Persisting CAR-T generate sustained pressure against that may drive unique mechanisms of resistance. Pre-B ALL originates from a committed pre-B cell or an earlier progenitor, with potential to reprogram into other hematopoietic lineages. Here we report changes markers including...
Autologous T cells engineered to express a chimeric antigen receptor (CAR) against the CD19 are in frontline of contemporary hemato-oncology therapies, leading high remission rates B-cell malignancies. Although effective, major obstacles involve complex and costly individualized manufacturing process, target loss or modulation resistant relapse following CAR therapy. A potential solution for these limitations is use donor-derived γδT as backbone. lack allogenecity safely used haploidentical...
// Ariel Bier, 1 Nis Giladi, Noam Kronfeld, Hae Kyung Lee, 2 Simona Cazacu, Susan Finniss, Cunli Xiang, Laila Poisson, 3 Ana C. deCarvalho , Shimon Slavin 4 Elad Jacoby, 5 Michal Yalon, Amos Toren, Tom Mikkelsen and Chaya Brodie 1,2 Everard Mina Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel, Davidson Laboratory Cell Signaling Tumorigenesis, Hermelin Brain Tumor Center, Department Neurosurgery, Henry Ford Hospital, Detroit MI USA. Public Health Tel Aviv, Israel The...
TCR engagement induces CD8 CAR T cell exhaustion and poor in vivo functionality mice.
Some solid tumors have reduced posttranscriptional RNA editing by adenosine deaminase acting on (ADAR) enzymes, but the functional significance of this alteration has been unclear. Here, we found primary RNA-editing enzyme ADAR1 is frequently in metastatic melanomas. In situ analysis melanoma samples using progression tissue microarrays indicated a substantial downregulation during transition. Further, knockdown altered cell morphology, promoted vitro proliferation, and markedly enhanced...
Abstract On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) approved tisagenlecleucel (KYMRIAH, Novartis, Basel, Switzerland ), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor-T cells (CAR-T), for treatment children young adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). With this new era personalized cancer immunotherapy, multiple challenges are present ranging from implementation CAR-T program to safe delivery drug, long-term...
Glioblastomas (GBM), the most common and aggressive type of malignant glioma, are characterized by increased invasion into surrounding brain tissues. Despite intensive therapeutic strategies, median survival GBM patients has remained dismal over last decades. In this study we examined expression miR-145 in glial tumors its function glioma cells. Using TCGA analysis real-time PCR found that miR-145/143 cluster was downregulated astrocytic compared to normal specimens cells stem (GSCs)...
Abstract Autologous CD19 chimeric‐antigen receptor (CAR) T cells demonstrated remarkable remission rates in relapsed and refractory acute lymphoblastic leukemia (R/R ALL). Here, we report results from a phase 1b/2 study of in‐house produced CAR with CD28 costimulatory domain. Twenty‐one patients R/R ALL were enrolled, 20 infused. The median age was 11 years (range, 5‐48). Patients had 4 prior regimens, including blinatumomab 6 stem–cell transplantation 10. In total 8 extramedullary (EM)...
On August 30, 2017 the US Food and Drug Administration approved tisagenlecleucel (Kymriah; Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor T cells (CAR-T), for treatment children young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). With this new era personalized cancer immunotherapy, multiple challenges are present, ranging from implementation CAR-T program to safe delivery drug, long-term toxicity monitoring,...
Chimeric antigen receptor (CAR) T cells directed against CD19 (CART19) are effective in B-cell malignancies, but little is known about the molecular factors predicting clinical outcome of CART19 therapy. The increasingly recognized relevance epigenetic changes cancer immunology prompted us to determine impact DNA methylation profiles on course.We recruited 114 patients with comprising 77 acute lymphoblastic leukemia and 37 non-Hodgkin lymphoma who were treated cells. Using a comprehensive...
Background Adoptive cell therapy with T cells genetically engineered to express a chimeric antigen receptor (CAR-T) or tumor-infiltrating lymphocytes (TIL) demonstrates impressive clinical results in patients cancer. Lymphodepleting preconditioning prior infusion is an integral part of all adoptive therapies. However, date, there no standardization and data comparing different non-myeloablative (NMA) regimens. Methods In this study, we compared NMA therapies doses cyclophosphamide total body...
Patients with single large-scale mitochondrial DNA (mtDNA) deletion syndromes (SLSMDs) usually present multisystemic disease, either as Pearson syndrome in early childhood or Kearns-Sayre later life. No disease-modifying therapies exist for SLSMDs. We have developed a method to enrich hematopoietic cells exogenous mitochondria, and we treated six patients SLSMDs through compassionate use program. Autologous CD34 + were augmented maternally derived healthy technology termed augmentation...
Background CD19 chimeric antigen receptor T (CAR-T) cells demonstrate remarkable remission rates in pediatric and adult patients with refractory or relapsed (r/r) acute lymphoblastic leukemia (ALL) non-Hodgkin's lymphoma (NHL). In 2016, we initiated a clinical trial in-house produced CAR-T CD28 co-stimulatory domain. We analyzed, for the first time, differences production features phenotype between ALL NHL patients. Methods Non-cryopreserved were from patients’ peripheral blood mononuclear...
CAR T-cells are approved for the treatment of relapsed and refractory leukemia lymphoma. Here, we studied infectious complications in 88 patients treated with CD28-based CD19 T-cells. Overall, 36 infections were documented 24 within first month after T-cell infusion: Six events bacteremia, sixteen focal bacterial infections, fourteen systemic or localized viral infections. Seven had nine episodes beyond 30 days follow-up, including three bacterial, two one fungal infection. The presence...