A5064670126- Cytokine Signaling Pathways and Interactions
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Viral Infectious Diseases and Gene Expression in Insects
- interferon and immune responses
- Silicon Carbide Semiconductor Technologies
- T-cell and B-cell Immunology
- Urticaria and Related Conditions
- Melanoma and MAPK Pathways
- Integrated Circuits and Semiconductor Failure Analysis
- MicroRNA in disease regulation
- Peptidase Inhibition and Analysis
- Circular RNAs in diseases
- Angiogenesis and VEGF in Cancer
- Nanowire Synthesis and Applications
- Immune cells in cancer
- Biosimilars and Bioanalytical Methods
- Advancements in Semiconductor Devices and Circuit Design
- Multiple Myeloma Research and Treatments
- Epigenetics and DNA Methylation
Sheba Medical Center
2016-2025
Tel Aviv University
2008-2024
École Centrale Paris
2013
Cancer Research Center
2009-2013
Melanoma Institute Australia
2011
Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) has shown promising results in metastatic melanoma patients. Although objective response rates of over 50% have been reported, disadvantages this approach are the labor-intensive TIL production and a very high drop-out rate enrolled patients, limiting its widespread applicability. Previous studies showed clear correlation between short culture periods clinical response. Therefore, we used new technique using...
Abstract Purpose: Adoptive cell transfer (ACT) using autologous tumor-infiltrating lymphocytes (TIL) was reported to yield objective responses in about 50% of metastatic patients with melanoma. Here, we present the intent-to-treat analysis TIL ACT and analyze parameters predictive response as well impact other immunotherapies. Experimental Design: Eighty stage IV melanoma were enrolled, which 57 treated unselected/young high-dose interleukin-2 (IL-2) following nonmyeloablative...
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...
Treatment of metastatic melanoma patients with adoptively transferred tumor infiltrating lymphocytes (TIL) has developed into an effective therapy. Various studies reported objective responses 50% and more. The use unselected, minimally cultured, bulk TIL (Young-TIL) simplified the production process may therefore, allow accessibility this approach to cancer centers worldwide. This article describes precise leading large-scale Young-TIL for We have enrolled 55 optimized their generation...
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)...
Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) and high-dose interleukin-2 (IL-2), after nonmyeloablative chemotherapy, has been shown to result in tumor regression half of refractory metastatic melanoma patients. In the present study, we describe 2 separate clinical protocols. Twelve patients were treated “Selected”-TIL, as previously reported 8 modified version “Young”-TIL. Selected-TIL protocol required establishment multiple T-cell cultures from 1 patient...
MicroRNAs (miRNAs) are small non-coding RNAs with regulatory roles, which involved in a broad spectrum of physiological and pathological processes, including cancer. A common strategy for identification miRNAs cell transformation is to compare malignant cells normal cells. Here we focus on that regulate the aggressive phenotype melanoma To avoid differences due genetic background, comparative high-throughput miRNA profiling was performed two isogenic human lines display major their net...
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...
// Gilli Galore-Haskel 1, 4 , Yael Nemlich 1 Eyal Greenberg Shira Ashkenazi Motti Hakim 5 Orit Itzhaki Noa Shoshani Ronnie Shapira-Fromer Eytan Ben-Ami Efrat Ofek 2 Liat Anafi Michal J. Besser Jacob Schachter * Gal Markel 3, 4, Ella Lemelbaum Institute of Melanoma, Sheba Medical Center, Israel Pathology, 3 Talpiot Leadership Program, Department Clinical Microbiology and Immunology, Tel Aviv University, Aviv, cCAM Biotherapeutics, Misgav Industrial Park, Misgav, These authors have contributed...
Adoptive cell therapy (ACT) of autologous Tumor Infiltration T Lymphocytes (TIL) is an effective immunotherapy for patients with solid tumors, yielding objective response rates around 40% in refractory metastatic melanoma. Most clinical centers utilize bulk, randomly isolated TIL from the tumor tissue ex vivo expansion and infusion. Only a minor fraction administered cells recognizes antigens, such as shared mutation-derived neoantigens, consequently eliminates tumor. Thus, there are many...
Vasculogenic mimicry (VM) describes functional vascular channels composed only of tumor cells and its presence predicts poor prognosis in melanoma patients. Inhibition this alternative vascularization pathway might be clinical importance, especially as several anti-angiogenic therapies targeting endothelial are largely ineffective melanoma. We show the VM structures histologically a series human lesions demonstrate that cell cultures derived from these form tubes 3D ex vivo. tested ability...
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...
Advanced prostate cancer remains incurable and is the second leading cause of mortality in men. Immunotherapy based on adoptive transfer tumor-infiltrating lymphocytes (TIL) has demonstrated promising clinical results patients with metastatic melanoma lately also other solid tumors. However, ability to obtain TIL from cancer, considered poorly immunogenic, unknown. In this study, we investigate feasibility isolating expanding primary We collected tumor specimens eight diagnosed...
CD28-based CD19 chimaeric antigen receptor-modified (CAR-)Tcells were recently FDA-approved for adult acute lymphoblastic leukaemia (ALL). We report long-term outcome of 37 children and young adults treated with autologous CAR-T cells. The complete remission rate was 86%, which 71% polymerase chain reaction (PCR) minimal residual disease (MRD)-negative, 14% MRD-negative by flow cytometry, PCR MRD-positive. 26 patients proceeded to subsequent haematopoietic stem cell transplant (HSCT). 11 had...
Quantification of circulating microRNAs (miRNAs) has recently become feasible and reliable, with most efforts focusing on miRNAs overexpressed by cancer cells.Identification a characteristic profile in melanoma patients.We conducted pilot study comprised unbiased qPCR comparison serum miRNA profiles between metastatic patients healthy donors.Loss two normal serum-miRNAs, miR-29c miR-324-3p, is highly indicative melanoma. Hierarchical clustering analysis supported the results clearly...
Abstract Adoptive cell transfer (ACT) of tumor‐infiltrating lymphocytes (TIL) mediates objective responses in 30% to 50% patients with metastatic melanoma according multiple, small phase 2 trials. Here we report the long‐term clinical results, intent‐to‐treat analysis, predictors response and toxicity profile a large patient cohort. A total 179 refractory were enrolled ACT trial. TIL administered combination high‐dose bolus interleukin‐2 following preconditioning cyclophosphamide...
Despite the high rates of complete remission following chimeric antigen receptor (CAR) T cell therapy, its full capacity is currently limited by generation dysfunctional CAR cells. Senescent or exhausted cells possess poor targeting and effector functions, as well impaired proliferation persistence in vivo. Strategies to detect, prevent reverse exhaustion are therefore required order enhance effectiveness immunotherapy. Here we report that CD19 from non-responding patients with B...
Adoptive cell therapy with chimeric antigen receptor (CAR) T cells has become an efficient treatment option for patients hematological malignancies. FDA approved CAR products are manufactured in centralized facilities from fresh or frozen leukapheresis and the cryopreserved infusion product is shipped back to patient. An increasing number of clinical centers produce on-site, which enables use PBMCs cells. Here we determined effect cryopreservation on CD19 a cohort 118 treated several...