A5028969206- CAR-T cell therapy research
- DNA Repair Mechanisms
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- MicroRNA in disease regulation
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Immune Cell Function and Interaction
- Nanowire Synthesis and Applications
- T-cell and B-cell Immunology
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Neuroblastoma Research and Treatments
- Multiple Myeloma Research and Treatments
- BRCA gene mutations in cancer
- Telomeres, Telomerase, and Senescence
- Chronic Lymphocytic Leukemia Research
- Immune cells in cancer
- Acute Lymphoblastic Leukemia research
- Cellular transport and secretion
- Biosimilars and Bioanalytical Methods
- Autophagy in Disease and Therapy
- Integrated Circuits and Semiconductor Failure Analysis
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2017-2025
Hospital Clínic de Barcelona
2018-2025
Universitat de Barcelona
2022-2025
Fundació Clínic per a la Recerca Biomèdica
2025
Hospital Sant Joan de Déu Barcelona
2022-2024
Banc de Sang i Teixits
2020-2021
Josep Carreras Leukaemia Research Institute
2017-2020
Institute for Biomedicine
2020
Fred Hutch Cancer Center
2011-2017
Howard Hughes Medical Institute
2012-2015
We evaluated the administration of ARI-0001 cells (chimeric antigen receptor T targeting CD19) in adult and pediatric patients with relapsed/refractory CD19+ malignancies. Patients received cyclophosphamide fludarabine followed by at a dose 0.4-5 × 106 cells/kg, initially as single later split into 3 fractions (10%, 30%, 60%) full depending on absence cytokine release syndrome (CRS). 58 were included, which 47 therapy: 38 acute lymphoblastic leukemia (ALL), 8 non-Hodgkin's lymphoma, 1...
Development of semi-automated devices that can reduce the hands-on time and standardize production clinical-grade CAR T-cells, such as CliniMACS Prodigy from Miltenyi, is key to facilitate development T-cell therapies, especially in academic institutions. However, feasibility manufacturing products heavily pre-treated patients with this system has not been demonstrated yet. Here we report characterize 28 context a phase I clinical trial for CD19+ B-cell malignancies (NCT03144583). The...
Genetically modifying autologous T cells to express an anti-CD19 chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19+ B cell malignancies in several clinical trials (CTs). Making this available our patients prompted us develop a novel CART19 based on own antibody (A3B1), followed by CD8 hinge and transmembrane region, 4-1BB- CD3z-signaling domains. We show that A3B1 CAR are highly cytotoxic specific against vitro, inducing secretion pro-inflammatory...
Fanconi anemia is a recessively inherited disease that characterized by congenital abnormalities, bone marrow failure, and predisposition to develop cancer, particularly squamous cell carcinomas (SCCs) in the head neck anogenital regions. Previous studies of SCCs, mainly from US patients, revealed presence high-risk human papillomavirus (HPV) DNA 21 (84%) 25 tumors analyzed. We examined panel SCCs European patients (n = 19 FA patients; 16 [HNSCCs], 2 esophageal 3 SCCs) for their clinical...
The Fanconi anemia (FA)-BRCA pathway mediates repair of DNA interstrand crosslinks. FA core complex, a multi-subunit ubiquitin ligase, participates in the detection lesions and monoubiquitinates two downstream proteins, FANCD2 FANCI (or ID complex). However, regulation complex itself is poorly understood. Here we show that proteins are recruited to sites damage form nuclear foci S G2 phases cell cycle. ATR kinase activity, an intact FANCM-FAAP24 were crucial for this recruitment....
Background Acute myeloid leukemia (AML) is a hematopoietic malignancy which biologically, phenotypically and genetically very heterogeneous. Outcome of patients with AML remains dismal, highlighting the need for improved, less toxic therapies. Chimeric antigen receptor T-cell (CART) immunotherapies refractory or relapse (R/R) are challenging because absence universal pan-AML target shared expression antigens normal stem/progenitor cells (HSPCs), may lead to life-threating on-target/off-tumor...
Abstract The tumor suppressor p53 and miRNAs are linked through a complex network. Several modulate expression, while regulates the transcription and/or biogenesis of several other miRNAs. Here, we report development cell-based assay used with library human miRNA mimics in high-throughput screen for that expression. Overexpression (miR)-542-3p cancer cells elevated stimulated expression targets, inhibited cell proliferation. Mechanistically, miR-542-3p increased protein stability by...
Chimeric antigen receptor (CAR)-modified T cells have revolutionized the treatment of CD19-positive hematologic malignancies. Although anti-CD19 CAR-engineered autologous can induce remission in patients with B-cell acute lymphoblastic leukemia, a large subset relapse, most them disease. Therefore, new therapeutic strategies are clearly needed. Here, we report comprehensive study comparing engineered either expressing second-generation CAR (CAR-T19) or secreting CD19/CD3-targeting bispecific...
Multiple myeloma is a prevalent and incurable disease, despite the development of new effective drugs. The recent chimeric antigen receptor (CAR)-T cell therapy has shown impressive results in treatment patients with relapsed or refractory hematological B malignancies. In years, B-cell maturation (BCMA) appeared as promising to target using variety immuno-therapy treatments including CART cells, for MM patients. To this end, we generated clinical-grade murine cells directed against BCMA,...
Fanconi anaemia is a heterogeneous genetic disease, where 12 complementation groups have been already described. Identifying the group in patients with constitutes direct procedure to confirm diagnosis of disease and required for recruitment these gene therapy trials.To determine subtype Spain, Mediterranean country relatively high population (23%) belonging gypsy race.Most could be subtyped by retroviral approaches peripheral blood T cells, although some mosaic were cultured skin...
Repair of interstrand crosslinks by the Fanconi anemia (FA) pathway requires both monoubiquitination and de-ubiquitination FANCI/FANCD2 (FANCI/D2) complex. In standing model, phosphorylation six sites in FANCI S/TQ cluster domain occurs upstream of, promotes, FANCI/D2 monoubiquitination. We generated phospho-specific antibodies against three different (serines 556, 559, 565) on human found that, contrast to distinct were phosphorylated either predominantly (ubiquitination independent; serine...
Anti-CD19 chimeric antigen receptor (CAR)-T cells have achieved impressive outcomes for the treatment of relapsed and refractory B-lineage neoplasms. However, important limitations still remain due to severe adverse events (i.e., cytokine release syndrome neuroinflammation) relapse 40%-50% treated patients. Most CAR-T are generated using retroviral vectors with strong promoters that lead high CAR expression levels, tonic signaling, premature exhaustion, overstimulation, reducing efficacy...
Background/Objectives: Potency testing of clinical-grade lentiviral vectors (LVVs) is critical to support a drug’s commercial approval. Careful consideration should be paid the development suitable potency test during clinical development. We aimed develop an affordable, quantitative for our CAR19-LVV, based on measure transgene’s functional activity. Methods: Several indicators activity CAR19-LVV were explored in co-culture setting CAR-transduced Jurkat cells and CD19-expressing target...
Abstract The endo-lysosomal phospholipid, bis(monoacylglycerol)phosphate (BMP), is aberrantly elevated in the urine of Parkinson’s patients with mutations genes encoding leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GCase). Because BMP resides on regulates biogenesis intralumenal membranes that become extracellular vesicles (EVs) upon release, we hypothesized urinary may be driven by increased exocytosis BMP-enriched EVs. To test this hypothesis, analyzed metabolism...
Abstract The endo-lysosomal phospholipid, bis(monoacylglycerol)phosphate (BMP), is aberrantly elevated in the urine of Parkinson’s patients with mutations genes encoding leucine-rich repeat kinase 2 (LRRK2) and glucocerebrosidase (GCase). Because BMP resides on regulates biogenesis intralumenal membranes that become extracellular vesicles (EVs) upon release, we hypothesized urinary may be driven by increased exocytosis BMP-enriched EVs. To test this hypothesis, analyzed metabolism...
Proteins essential for homologous recombination play a pivotal role in the repair of DNA double strand breaks, inter-strand crosslinks and replication fork stability. Defects also critical development cancer sensitivity these cancers to chemotherapy. RAD51, an factor protection, accumulates forms immunocytochemically detectable nuclear foci at sites damage. To identify kinases that may regulate RAD51 localization damage, we performed human kinome siRNA library screen, using damage-induced...
Autologous T cells expressing the Chimeric Antigen Receptor (CAR) have been approved as advanced therapy medicinal products (ATMPs) against several hematological malignancies. However, generation of patient-specific CAR-T delays treatment and precludes standardization. Allogeneic off-the-shelf are an alternative to simplify this complex time-consuming process. Here we investigated safety efficacy knocking out TCR molecule in ARI-0001 cells, a second αCD19 CAR by Spanish Agency Medicines...