A5009273420- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Chemokine receptors and signaling
- Nanoparticle-Based Drug Delivery
- Immune Cell Function and Interaction
- Acute Myeloid Leukemia Research
- Glycosylation and Glycoproteins Research
- Toxin Mechanisms and Immunotoxins
- RNA Interference and Gene Delivery
- Cancer Research and Treatments
- Galectins and Cancer Biology
- Neuroblastoma Research and Treatments
- Virus-based gene therapy research
- Multiple Myeloma Research and Treatments
- Lymphoma Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- Vascular Tumors and Angiosarcomas
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Mechanisms and Therapy
- Protein Degradation and Inhibitors
- Advanced biosensing and bioanalysis techniques
- Biomedical and Engineering Education
- Viral Infectious Diseases and Gene Expression in Insects
- Signaling Pathways in Disease
Josep Carreras Leukaemia Research Institute
2020-2025
Instituto de Salud Carlos III
2023-2024
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine
2019-2023
Hospital de Sant Pau
2018-2023
Institut d'Investigació Biomédica de Bellvitge
2021-2022
Fundación Josep Carreras Contra la Leucemia
2021
Universitat Autònoma de Barcelona
2021
Biomedical Research Institute
2019
Multiple myeloma is the second most common hematological malignancy in adults and remains an incurable disease. B cell maturation antigen (BCMA)–directed immunotherapy, including T cells bearing chimeric receptors (CARs) systemically injected bispecific engagers (TCEs), has shown remarkable clinical activity, several products have received market approval. However, despite promising results, patients eventually become refractory relapse, highlighting need for alternative strategies....
Abstract Background Current acute myeloid leukemia (AML) therapy fails to eliminate quiescent leukemic blasts in the bone marrow, leading about 50% of patient relapse by increasing AML burden blood, and extramedullar sites. We developed a protein-based nanoparticle conjugated potent antimitotic agent Auristatin E that selectively targets because their CXCR4 receptor overexpression (CXCR4+) as compared normal cells. The therapeutic rationale is based on involvement blast homing quiescence...
Abstract Functional amyloids produced in bacteria as nanoscale inclusion bodies are intriguing but poorly explored protein materials with wide therapeutic potential. Since they release functional polypeptides under physiological conditions, these can be potentially tailored mimetic of secretory granules for slow systemic delivery smart drugs. To explore this possibility, bacterial formed by a self‐assembled, tumor‐targeted Pseudomonas exotoxin (PE24) administered subcutaneously mouse models...
One-third of diffuse large B-cell lymphoma patients are refractory to initial treatment or relapse after rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy. In these patients, CXCR4 overexpression (CXCR4+) associates with lower overall disease-free survival. Nanomedicine pursues active targeting selectively deliver antitumor agents cancer cells; a novel approach that promises revolutionize therapy by dramatically increasing drug concentration in target...
Relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) remains a challenging disease with dismal prognosis. Despite the revolutionary impact of CD19-directed chimeric antigen receptor (CAR19)-T cell therapy, >50% patients relapse within year. Both cell-intrinsic factors favoring immune escape and poor CAR-T persistence contribute significantly to clinical failure. Moreover, expression checkpoint receptors (ICRs) their ligands complex bone marrow (BM) microenvironment...
Abstract Under the unmet need of efficient tumor‐targeting drugs for oncology, a recombinant version plant toxin ricin (the modular protein T22‐mRTA‐H6) is engineered to self‐assemble as protein‐only, CXCR4‐targeted nanoparticles. The soluble construct self‐organizes regular 11 nm planar entities that are highly cytotoxic in cultured CXCR4 + cancer cells upon short time exposure, with determined IC50 nanomolar order magnitude. chemical inhibition binding sites exposed results dramatic...
Fluorescent dye labeling is a common strategy to analyze the fate of administered nanoparticles in living organisms. However, which extent processes can alter original nanoparticle biodistribution has been so far neglected. In this work, two widely used fluorescent molecules, namely, ATTO488 (ATTO) and Sulfo-Cy5 (S-Cy5), have covalently attached well-characterized CXCR4-targeted self-assembling protein (known as T22-GFP-H6). The labeled T22-GFP-H6-ATTO T22-GFP-H6-S-Cy5 then compared that...
Despite advances in the development of targeted therapies for acute myeloid leukemia (AML), most patients relapse. For that reason, it is still necessary to develop novel improve treatment effectiveness and overcome drug resistance. We developed T22-PE24-H6, a protein nanoparticle contains exotoxin A from bacterium Pseudomonas aeruginosa able specifically deliver this cytotoxic domain CXCR4+ leukemic cells. Next, we evaluated selective delivery antitumor activity T22-PE24-H6 AML cell lines...
Background and Purpose: Around 40– 50% of diffuse large-B cell lymphoma (DLBCL) patients suffer from refractory disease or relapse after R-CHOP first-line treatment. Many ongoing clinical trials for DLBCL involve microtubule targeting agents (MTAs), however, their anticancer activity is limited by severe side effects. Therefore, we chose to improve the therapeutic window MTA monomethyl auristatin E developing a nanoconjugate, T22-AUR, that selectively targets CXCR4 receptor, which...
Current therapy in acute myeloid leukemia (AML) is based on chemotherapeutic drugs administered at high doses, lacking targeting selectivity and displaying poor therapeutic index because of severe adverse effects. Here, we develop a novel nanoconjugate that combines self-assembled, multivalent protein nanoparticle, the CXCR4 receptor, with an Oligo-Ara-C prodrug, pentameric form Ara-C, to highly increase delivered payload target cells. This 13.4 nm T22-GFP-H6-Ara-C selectively eliminates...
Background: Novel therapeutic strategies are urgently needed to reduce relapse rates and enhance survival in Diffuse Large B-Cell Lymphoma (DLBCL) patients. CXCR4-overexpressing cancer cells good targets for therapy because of their association with dissemination R-CHOP treated DLBCL Immunotoxins that incorporate bacterial toxins potentially effective treating haematological neoplasias, but show a narrow index due the induction severe side effects. Therefore, when considering delivery these...
The sustained release of small, tumor-targeted cytotoxic drugs is an unmet need in cancer therapies, which usually rely on punctual administration regimens non-targeted drugs. Here, we have developed a novel concept protein-drug nanoconjugates, are packaged as slow-releasing chemically hybrid depots and sustain prolonged secretion the therapeutic agent. For this, covalently attached hydrophobic molecules (including antitumoral drug Monomethyl Auristatin E) to protein targeting tumoral cell...
The accumulated molecular knowledge about human cancer enables the identification of multiple cell surface markers as highly specific therapeutic targets. A proper tumor targeting could significantly avoid drug exposure healthy cells, minimizing side effects, but it is also expected to increase index. Specifically, colorectal has a particularly poor prognosis in late stages, being an appropriate strategy substantially improve efficacy. In this study, we have explored potential...
Humanized immunodeficient mice serve as critical models for investigating the functional interplay between transplanted human cells and a pre-reconstituted immune system. These facilitate study of molecular cellular pathogenic mechanisms enable evaluation efficacy toxicity immunotherapies, thereby accelerating their preclinical clinical development. Current strategies rely on inefficient, long-term/delayed hematopoietic reconstitution by CD34+ progenitors or short-term with peripheral blood...
The CXCR4/CXCL12 axis has been extensively associated with different types of cancer correlating higher aggressiveness and metastasis. In diffuse large B-cell lymphoma (DLBCL), the expression chemokine receptor CXCR4 is involved in dissemination malignant B cells a marker poor prognosis. CXCR7 that binds to same ligand as regulates de CXCR4-CXCL12 axis. These findings together report prognostic value several tumor types, led us evaluate biopsies. Here, we describe an independent factor...
High rates of relapsed and refractory diffuse large B-cell lymphoma (DLBCL) patients life-threatening side effects associated with immunochemotherapy make an urgent need to develop new therapies for DLBCL patients. Immunotoxins seem very potent anticancer but their use is limited because high toxicity. Accordingly, the self-assembling polypeptidic nanoparticle, T22-DITOX-H6, incorporating diphtheria toxin targeted CXCR4 receptor, which overexpressed in cells, could offer a strategy...
In recent years, several attempts have been made to identify novel prognostic markers in patients with intermediate-risk acute myeloid leukemia (IR-AML), implement risk-adapted strategies. The non-receptor tyrosine kinases are proteins involved regulation of cell growth, adhesion, migration and apoptosis. They associate metastatic dissemination solid tumors poor prognosis. However, their role haematological malignancies has scarcely studied. We hypothesized that PTK2/FAK, PTK2B/PYK2, LYN or...
2550 Background: Antigen-specific cancer immunotherapies, based on engineered T cells bearing chimeric antigen receptors (CARs) or the systemic administration of bispecific cell-engagers (TCEs), have a significant impact relapsed/refractory (R/R) B cell malignancies. However, percentage patients relapse following CAR-T TCE therapy, with loss accounting for up to one third relapses/progressions. To avoid after single-targeted and minimize tumor escape, strategies targeting two antigens...
ABSTRACT T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy characterized by high rates of induction failure and relapse, effective targeted immunotherapies are lacking. Despite promising clinical progress with genome-edited CD7-directed CAR-T cells, which present significant logistical regulatory issues, therapy in T-ALL remains challenging due to the shared antigen expression between malignant healthy cells. This can result fratricide, aplasia, potential for blast...
One-year relapse rates of leukemia patients treated with CD19-targeted CAR-T cells (CAR19T) are >60% partly due to CAR19T intrinsic mechanisms and their interaction leukemic microenvironment. Here, we have comprehensively characterized the expression inhibitory immune checkpoint receptors (ICRs) in T-cells, ligands both mesenchymal stromal (MSC) from bone marrow (BM) pediatric adult primary B-cell acute lymphoblastic (ALL) at diagnosis relapse. Among all ICRs-ligands analyzed, our results...