A5077791294- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Cancer Research and Treatments
- Virus-based gene therapy research
- Immune cells in cancer
- Viral Infections and Vectors
- Mosquito-borne diseases and control
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nanoplatforms for cancer theranostics
- Cancer, Hypoxia, and Metabolism
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- interferon and immune responses
- Viral Infections and Outbreaks Research
- S100 Proteins and Annexins
- Lung Cancer Research Studies
- Galectins and Cancer Biology
- Viral Infectious Diseases and Gene Expression in Insects
- Glioma Diagnosis and Treatment
- Effects of Radiation Exposure
- Cancer Mechanisms and Therapy
- Animal Disease Management and Epidemiology
Clinica Universidad de Navarra
2013-2025
Universidad de Navarra
2014-2024
Navarre Institute of Health Research
2015-2024
Chartered Institute of Management Accountants
2014-2023
University of Lausanne
2018-2023
Foundation for Medical Research
2022
Pediatrics and Genetics
2022
Gene Therapy Laboratory
2015
Bipar
2014
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2013
Weak and ineffective antitumor cytotoxic T lymphocyte (CTL) responses can be rescued by immunomodulatory mAbs targeting PD-1 or CD137. Using Batf3(-/-) mice, which are defective for cross-presentation of cell-associated antigens, we show that BATF3-dependent dendritic cells (DC) essential the response to therapy with anti-CD137 anti-PD-1 mAbs. mice failed prime an endogenous CTL-mediated immune toward tumor-associated including neoantigens. As a result, could not amplify any therapeutically...
Abstract Purpose: Myeloid-derived suppressor cells (MDSC) are considered an important T-cell immunosuppressive component in cancer-bearing hosts. The factors that attract these to the tumor microenvironment poorly understood. IL8 (CXCL8) is a potent chemotactic factor for neutrophils and monocytes. Experimental Design: MDSC were characterized sorted by multicolor flow cytometry on ficoll-gradient isolated blood leucokytes from healthy volunteers (n = 10) advanced cancer patients 28). In...
Abstract Preclinical and clinical evidence indicate that the proimmune effects of radiotherapy can be synergistically augmented with immunostimulatory mAbs to act both on irradiated tumor lesions distant, nonirradiated sites. The combination anti-PD1 anti-CD137 was conducive favorable distant as observed in transplanted MC38 (colorectal cancer), B16OVA (melanoma), 4T1 (breast cancer) models. therapeutic activity crucially performed by CD8 T cells, found selective depletion experiments....
Pediatric patients with diffuse intrinsic pontine glioma (DIPG) have a poor prognosis, median survival of less than 1 year. Oncolytic viral therapy has been evaluated in pediatric gliomas elsewhere the brain, but data regarding oncolytic DIPG are lacking.
Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain stem tumor and the leading cause of pediatric cancer-related death. To date, these tumors remain incurable, underscoring need for efficacious therapies. In this study, we demonstrate that immune checkpoint TIM-3 (HAVCR2) highly expressed in both cells microenvironmental cells, mainly microglia macrophages, DIPG. We show inhibition syngeneic models DIPG prolongs survival produces long-term survivors free disease harbor memory....
Abstract A current pressing need in cancer immunology is the development of preclinical model systems that are immunocompetent for study human tumors. Here, we report a humanized murine can be used to analyze pharmacodynamics and antitumor properties immunostimulatory monoclonal antibodies (mAb) settings where receptors targeted by mAbs expressed. Human lymphocytes transferred into immunodeficient mice underwent activation redistribution organs, they exhibited cell-surface expression hCD137...
Abstract Virotherapy and checkpoint inhibitors can be combined for the treatment of cancer with complementarity potential synergistic effects. We have developed a cytolytic but nonreplicative viral vector system based on Semliki Forest virus that encodes IL12 (SFV-IL12). Following direct intratumoral injection, infected cells release transgenic IL12, die, elicit an inflammatory response triggered by both abundantly copied RNA IL12. In difficult-to-treat mouse models, such as those derived...
Significance Immunotherapy of cancer with immunomodulatory agents is achieving significant efficacy in an important fraction patients. The stimulatory inducible receptor T and NK lymphocytes known as CD137 or 4-1BB being stimulated agonist antibodies to enhance antitumor immunity clinical trials. In addition, the intracellular signaling domain crucial a component successful anti-leukemia therapies chimeric antigen receptors transduced into adoptively transferred lymphocytes. this study...
Background More efficient therapeutic options for non-small cell lung cancer (NSCLC) are needed as the survival at 5 years of metastatic disease is near zero. In this regard, we used a preclinical model adenocarcinoma (SV2-OVA) to assess safety and efficacy novel radio-immunotherapy combining hypofractionated radiotherapy (HRT) with muPD1-IL2v immunocytokine muFAP-CD40 bispecific antibody. Methods We evaluated changes in immune microenvironment multiple timepoints following combination...
Immunostimulatory monoclonal antibodies (ISmAb) that unleash antitumor immune responses are showing efficacy in cancer clinical trials. Anti-B7-H1 (PD-L1) (mAb) block a critical inhibitory pathway T cells, whereas anti-CD137 and OX40 mAbs provide T-cell costimulation. A combination of these ISmAbs (anti-CD137 + anti-OX40 anti-B7-H1) was tested using transgenic mouse model multifocal rapidly progressing hepatocellular carcinoma, which c-myc drives transformation cytosolic ovalbumin (OVA) is...
T and NK lymphocytes express CD137 (4-1BB), a costimulatory receptor of the TNFR family whose function is exploitable for cancer immunotherapy. Mitochondria regulate survival lymphocytes. Herein, we show that costimulation provided by agonist mAb CD137L (4-1BBL) induced mitochondria enlargement resulted in enhanced mitochondrial mass transmembrane potential human mouse CD8+ cells. Such changes increased T-cell respiratory capacities were critically dependent on fusion protein OPA-1...
: Multiple lines of evidence indicate a critical role antigen cross-presentation by conventional BATF3-dependent type 1 classical dendritic cells (cDC1) in CD8-mediated antitumor immunity. Flt3L and XCL1, respectively, constitute key growth/differentiation factor potent specific chemoattractant for cDC1. To exploit their functions local immunotherapy, we prepared Semliki Forest Virus (SFV)-based vectors encoding XCL1 soluble (sFlt3L). These readily conferred transgene expression to the tumor...
Abstract Purpose: CD40 agonists hold great promise for cancer immunotherapy (CIT) as they enhance dendritic cell (DC) activation and concomitant tumor-specific T-cell priming. However, the broad expression of accounts sink side effects, hampering efficacy anti-CD40 antibodies. We hypothesized that these limitations can be overcome by selectively targeting agonism to tumor. Therefore, we developed a bispecific FAP-CD40 antibody, which induces stimulation solely in presence fibroblast protein...
Hypoxia is a common feature in solid tumors that has been implicated immune evasion. Previous studies from our group have shown hypoxia upregulates the co-stimulatory receptor CD137 on activated T lymphocytes and vascular endothelial cells. In this study, we show exposure of mouse human tumor cell lines to hypoxic conditions (1% O2) promotes transcription. However, resulting mRNA predominantly an alternatively spliced form encodes for soluble variant, lacking transmembrane domain....
Background Glioblastoma (GBM) is a devastating primary brain tumor with highly immunosuppressive microenvironment, and treatment oncolytic viruses (OVs) has emerged as promising strategy for these tumors. Our group constructed new OV named Delta-24-ACT, which was based on the Delta-24-RGD platform armed 4-1BB ligand (4-1BBL). In this study, we evaluated antitumor effect of Delta-24-ACT alone or in combination an immune checkpoint inhibitor (ICI) preclinical models glioma. Methods The vitro...
CD137 (4-1BB) costimulation imprints long-term changes that instruct the ultimate behavior of T cells have previously experienced ligation. Epigenetic could provide a suitable mechanism for these consequences. Genome-wide DNA methylation arrays were carried out on human peripheral blood CD8+ lymphocytes stimulated with agonist monoclonal antibody to CD137, including urelumab, which is in phase I/II clinical trials cancer immunotherapy. Several genes showed consistent patterns response...
In the context of adoptive T cell transfer (ACT) for cancer treatment, it is crucial to generate in vitro large amounts tumor-specific CD8 cells with high potential persist vivo. PD-1, Tim3 and CD39 have been proposed as markers tumor-infiltrating lymphocytes (CD8 TILs). However, these molecules are highly expressed by terminally differentiated exhausted (Tex) that lack proliferation potential. Therefore, optimized strategies isolate TILs proliferative potential, such Tcf1+ precursor (Tpe)...
Abstract Purpose: The incidence of human papillomavirus–associated head and neck squamous cell carcinoma (HPV+-HNSCC) is rising worldwide although current therapeutic modalities are efficient in the majority patients, there a high rate treatment failures. Thus, novel combination approaches urgently needed to achieve better disease control patients with HPV+-HNSCC. We investigated safety efficacy fibroblast activation protein (FAP)-targeted CD40 agonist (FAP-CD40) local hypofractionated...