A5014831048- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Protein Tyrosine Phosphatases
- Immunotherapy and Immune Responses
- Galectins and Cancer Biology
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Cellular Mechanics and Interactions
- Advanced Fluorescence Microscopy Techniques
- RNA Interference and Gene Delivery
- Immune Response and Inflammation
- Microtubule and mitosis dynamics
- Advanced Biosensing Techniques and Applications
- Nuclear Structure and Function
- Nanowire Synthesis and Applications
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Cell Image Analysis Techniques
- CRISPR and Genetic Engineering
- Cell Adhesion Molecules Research
- Cellular transport and secretion
- Immune cells in cancer
- Complement system in diseases
- Phagocytosis and Immune Regulation
Research Institute Hospital 12 de Octubre
2012-2025
Universidad Complutense de Madrid
2016-2025
Max Planck Institute of Molecular Physiology
2008-2018
In-Q-Tel
2012
Max Planck Society
2009-2011
University of Cambridge
2005-2009
California State University, Long Beach
2008
Hospital Universitario de La Princesa
2001-2006
Universidad Autónoma de Madrid
2000-2005
Centro de Biología Molecular Severo Ochoa
2004
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....
The redirection of T cell activity using bispecific antibodies is one the most promising cancer immunotherapy approaches currently in development, but it limited by cytokine storm-related toxicities, as well pharmacokinetics and tumor-penetrating capabilities current antibody formats. Here, we have engineered ATTACK (Asymmetric Tandem Trimerbody for Activation Cancer Killing), a novel cell-recruiting which combines three EGFR-binding single-domain (VHH; clone EgA1) with single CD3-binding...
Retargeting of T lymphocytes toward cancer cells by bispecific antibodies has demonstrated its therapeutic potential, with one such antibody approved for the treatment acute lymphoblastic leukemia (blinatumomab) and several other in clinical trials. However, improvement their efficacy selectivity solid tumors is still required. Here, we describe a novel tandem T-cell recruiting trispecific colorectal (CRC). This construct, termed engager (TriTE), consists CD3-specific single-chain Fv (scFv)...
Although transfer of membrane proteins has been shown to occur during immune cell interactions, the functional significance this process is not well understood. Here we describe intercellular NKG2D and MHC class I chain-related molecule (MIC) B at cytotoxic natural killer synapse (cNK-IS). MICB expressed on 721.221 line induced clustering central supramolecular activation cluster, surrounded by a peripheral cluster containing F-actin. Moreover, (NK) membrane-connective structures formed...
Abstract The interaction of the activating receptor NKG2D with its ligands plays an important role in immunosurveillance tumors and infectious pathogens, but dysregulation this system may lead to autoimmunity. expression is induced by cellular “stress.” However, regulation these molecules not well understood. Here, we show that cells treated proteasome inhibitors can become more susceptible cytotoxicity mediated natural killer because induction for NKG2D, specifically ULBP2, down-regulation...
Fluorescence lifetime imaging microscopy (FLIM) can be used to quantify molecular reactions in cells by detecting fluorescence resonance energy transfer (FRET). Confocal FLIM systems based on time correlated single photon counting (TCSPC) methods provide high spatial resolution and sensitivity, but suffer from poor signal noise ratios (SNR) that complicate quantitative analysis. We extend a global analysis method, originally developed for frequency domain data, with new filtering method...
The proto-oncogenic epidermal growth factor receptor (EGFR) is a tyrosine kinase whose sensitivity to factors and signal duration determines cellular behavior. We resolve how EGFR's response (EGF) originates from dynamically established recursive interactions with spatially organized protein phosphatases (PTPs). Reciprocal genetic PTP perturbations enabled identification of receptor-like PTPRG/J at the plasma membrane ER-associated PTPN2 as major EGFR dephosphorylating activities. Imaging...
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...
Abstract Cell surface lectin receptors play important roles in the function of macrophages. Herein, we have identified and characterized human orthologue mouse Mcl / Clecsf8 .Human CLECSF8 codes for a type II membrane glycoprotein 215 amino acids that belongs to calcium‐dependent family (C‐type lectin). The cytoplasmic tail lacks consensus signaling motifs its extracellular region shows single carbohydrate recognition domain (CRD). gene has been localized on telomeric NK complex chromosome...
Highlights•LCK immune synapse focusing requires its strong interaction with ciliary UNC119A•ARL3Q71L results in unfocused LCK localization and increased T cell stimulation•The ARL3-GEF ARL13B localizes to the synapse•UNC119A regulatory arm interacts kinase domain a phosphoregulated mannerSummaryUpon engagement of receptor an antigen-presenting cell, initiates TCR signaling by phosphorylating activation motifs. However, mechanism specifically at is major question. We show that phosphorylation...
The crystal structures of the glycosylated N-terminal two domains ICAM-1 and ICAM-2 provided a framework for understanding role glycosylation in structure function intercellular adhesion molecules (ICAMs). most conserved glycans were less flexible structures, interacting with protein residues contributing to receptor folding expression. first N-linked glycan contacts an exposed tryptophan residue, defining glycan-W motif critical conformation integrin binding domain. absence this human...
Abstract The 2B4 molecule (CD244) has been described as a coreceptor in human NK cell activation. However, the behavior of during cytotoxic immune synapse (NK-IS) formation remains undetermined. In this study, we demonstrate redistribution and signaling adaptor molecule, lymphocyte activation molecule-associated protein (SAP), to NK-IS upon conjugates between resting cells EBV-infected 721.221 cells. Confocal microscopy showed that localized at central supramolecular cluster, surrounded by...
Abstract The MHC-encoded butyrophilin, BTN2A1, is a cell surface glycoprotein related to the extended family of B7 costimulatory molecules. BTN2A1 mRNA was expressed in most human tissues, but protein expression significantly lower leukocytes. An Ig-fusion bound immature monocyte-derived dendritic cells. Binding diminished upon MoDC maturation and no binding detected Langerhans Induction counterreceptor IL-4 dependent occurred early during differentiation. interaction required presence Ca2+...
T cell-redirection strategies aim to selectively eliminate cancer cells by physically linking lymphocytes with using tumor-targeted cell-cell bridging (CCB) molecules, such as membrane-anchored chimeric antigen receptors (CARs) or soluble bispecific antibodies (bsAbs) that specifically recognize a cell-surface tumor-associated (TAA) (Blanco et al., 2019). In the CAR approach, TAA-specific antibody is genetically fused intracellular cell signaling domains. CARs have evolved greatly since...
Significance New imaging-based approaches are incorporating new concepts to our knowledge of biological processes. The analysis receptor dynamics involved in cell movement using single-particle tracking demonstrates that cells require chemokine-mediated clustering sense appropriately chemoattractant gradients. Here, we report this process does not occur T expressing CXCR4 R334X , a mutant form linked WHIM syndrome (warts, hypogammaglobulinemia, infections, myelokathexis). underlaying...
Background CD19-directed cancer immunotherapies, based on engineered T cells bearing chimeric antigen receptors (CARs, CAR-T cells) or the systemic administration of bispecific cell-engaging (TCE) antibodies, have shown impressive clinical responses in relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, more than half patients relapse after TCE therapy, with escape lineage switching accounting for one-third disease recurrences. To minimize tumor escape, dual-targeting...
NKG2D is an important activating receptor for triggering the NK cell cytotoxic activity, although chronic engagement of specific ligands by also known to provoke decreased surface expression and compromised function. We have studied dynamics how exposure ligand major histocompatibility complex class I chain-related molecule B (MICB) affects traffic fate. While in NKL line "resting" cells was found principally at surface, activated primary intracellular pool could be recycling plasma...
The human NK gene complex localized on chromosome 12p12.3 – p13.2 codes for several lectin-like receptor genes expressed by cells as well other hematopoietic cells. In this study, using the sequence tag database we identified a novel gene, designated killer cell receptor, subfamily F, member 1 (KLRF1), encoding putative type II transmembrane glycoprotein. KLRF1 has been high-resolution physical map of 12p. genomic structure and existence one spliced variant are also described. was at mRNA...
Balanced activity of protein tyrosine kinases and phosphatases (PTPs) controls phosphorylation levels and, consequently, is needed to prevent pathologies like cancer. Phosphatase tightly regulated in space time. Thus, order understand how phospho-tyrosine signalling regulated, the intracellular dynamics PTPs should be investigated. Here, we have studied PTPD1, a FERM (four-point-one, ezrin, radixin, moesin) domain-containing PTP that over expressed cancer cells potentiates EGFR signalling....
Cancer immunotherapy strategies based on the endogenous secretion of T cell-redirecting bispecific antibodies by engineered lymphocytes (STAb-T) are emerging as alternative or complementary approaches to those chimeric antigen receptors (CAR-T). The antitumor efficacy anti-CD19 × anti-CD3 (CD19×CD3) cell engager (BiTE)-secreting STAb-T cells has been demonstrated in several mouse models B-cell acute leukemia. Here, we have investigated spatial topology and downstream signaling artificial...
Abstract We have characterized the lymphocyte subset and receptor molecules involved in inducing secretion of TNF by monocytic cells vitro . The secreted was measured when they were co-cultured with either resting or IL-15-stimulated lymphocytes, T cells, B natural killer (NK) isolated from peripheral blood healthy subjects synovial fluid patients inflammatory arthropathies. Co-culture IL-15-activated lymphocytes induced production within 24 hours, an effect that mainly mediated NK cells. In...