A5043314436- Immunotherapy and Immune Responses
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Galectins and Cancer Biology
- Glioma Diagnosis and Treatment
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Cancer Mechanisms and Therapy
- Lymphoma Diagnosis and Treatment
- Immune cells in cancer
- RNA modifications and cancer
- Glycosylation and Glycoproteins Research
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Multiple Myeloma Research and Treatments
- Immune Response and Inflammation
- Nanoplatforms for cancer theranostics
- Peptidase Inhibition and Analysis
- Adenosine and Purinergic Signaling
- Phagocytosis and Immune Regulation
- Animal Disease Management and Epidemiology
Universidad de Navarra
2016-2025
Navarre Institute of Health Research
2016-2025
Centro de Investigación Biomédica en Red de Cáncer
2022-2024
Complejo Hospitalario de Navarra
2015-2023
University of Miami
2008-2013
Sylvester Comprehensive Cancer Center
2011-2013
University of Iowa
2013
Hospital Universitario Virgen de la Arrixaca
2007
Centro de Investigación del Cáncer
2006
Universidad de Salamanca
2006
4-1BB is a major costimulatory receptor that promotes the survival and expansion of activated T cells. Administration agonistic anti–4-1BB Abs has been previously shown to enhance tumor immunity in mice. are cell-based products posing significant cost, manufacturing, regulatory challenges. Aptamers oligonucleotide-based ligands exhibit specificity avidity comparable to, or exceeding, Abs. To date, various aptamers have inhibit function their cognate target. Here, we described development an...
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 Background Prognosis of patients with glioblastoma multiforme (GBM) remains dismal, median overall survival (OS) about 15 months. It is therefore crucial to search alternative strategies that improve these results obtained conventional treatments. In this context, immunotherapy seems be a promising therapeutic option. We hypothesized the addition tumor lysate-pulsed autologous dendritic cells (DCs) vaccination maximal safe resection followed by radiotherapy and concomitant adjuvant...
The paucity of costimulation at the tumor site compromises ability tumor-specific T cells to eliminate tumor. Here, we show that bi-specific oligonucleotide aptamer conjugates can deliver costimulatory ligands in situ and enhance antitumor immunity. In poorly immunogenic subcutaneously implanted lung metastasis models, systemic delivery an agonistic 4-1BB ligand conjugated a prostate specific membrane antigen (PSMA)-binding tumor-targeting led inhibition growth, was more effective than,...
CD28 is one of the main costimulatory receptors responsible for proper activation T lymphocytes. We have isolated two aptamers that bind to receptor. As a monomer, them interfered with binding its ligand (B7), precluding signal, whereas other was inactive. However, dimerization any anti-CD28 sufficient provide an artificial signal. No antibody has featured dual function (i.e., ability work as agonist and antagonist) date. Two different agonistic structures were engineered each aptamer. One...
Follicular lymphoma is considered incurable, although cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy can induce sequential remissions. A patient's second complete response typically shorter than that first response. Idiotype vaccines elicit specific immune responses molecular remissions in patients with follicular lymphoma. However, a clinical benefit has never been formally proven.Thirty-three consecutive relapse received six monthly cycles of CHOP-like...
Abstract The paucity of costimulation at the tumor site compromises ability tumor-specific T cells to eliminate tumor. recent U.S. Food and Drug Administration approval ipilumimab, an antibody that blocks inhibitory action CTLA-4, clinical trials targeting 4-1BB PD-1 or PD-L1, have underscored therapeutic potential using immunomodulatory antibodies stimulate protective immunity in human patients. Nonetheless, systemic administration has been associated with dose-limiting autoimmune...
We report the first evaluation of plant-made conjugate vaccines for targeted treatment B-cell follicular lymphoma (FL) in a Phase I safety and immunogenicity clinical study. Each recombinant personalized immunogen consisted tumor-derived, plant-produced idiotypic antibody (Ab) hybrid comprising hypervariable regions tumor-associated light heavy Ab chains, genetically grafted onto common human IgG1 scaffold. was produced Nicotiana benthamiana plants using twin magnICON vectors expressing...
In this work we show a clinically feasible strategy to convert in situ the own tumor into an endogenous vaccine by coating melanoma cancerous cells with CD28 costimulatory ligands. This therapeutic approach is aimed at targeting T-cell costimulation chemotherapy-resistant tumors which are refractory and been considered as untreatable cancers. These usually defined enrichment of cancer stem characterized higher expression proteins. develop first aptamer that targets expressing MRP1 through...
Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) blockade therapy is able to induce long-lasting antitumor responses in a fraction of cancer patients. Nonetheless, there still room for improvement the quest new therapeutic combinations. ICOS costimulation has been underscored as possible target include with CTLA-4 blocking treatment. Herein, we describe an agonistic aptamer that potentiates cell activation and induces stronger when locally injected at tumor site combination anti-CTLA-4...
// Sandra Hervas-Stubbs 1, 2, * , Mario M. Soldevilla 3 Helena Villanueva Uxua Mancheño 2 Maurizio Bendandi 4 Fernando Pastor 3, 1 Program Immunology and Immunotherapy, Centro de Investigaciones Medicas Aplicadas (CIMA), Pamplona, Spain Instituto Investigación Sanitaria Navarra (IDISNA), Recinto Complejo Hospitalario Navarra, of Molecular Therapies, Aptamer Unit, Ross University School Medicine, Portsmouth, Commonwealth Dominica These authors have contributed equally to this...
Complementing Systematic Evolution of Ligands by EXponential Enrichment (SELEX) technologies with in silico prediction aptamer binders has attracted a lot interest the recent years. We propose workflow involving 2D structure prediction, 3D RNA modeling using Rosetta and docking to target protein 3dRPC for: (i) binding mode our two previously reported potent (Kd < 50 nmol/l) murine TIM3 aptamers, (ii) prioritization aptamers that were enriched SELEX workflow. The procedure was first validated...
Abstract Background The quality and quantity of tumor neoantigens derived from mutations determines the fate immune response in cancer. Frameshift elicit better neoantigens, especially when they are not targeted by nonsense-mediated mRNA decay (NMD). For progression, malignant cells need to counteract including silencing immunodominant (antigen immunoediting) promoting an immunosuppressive microenvironment. Although NMD inhibition has been reported induce immunity increase expression cryptic...
LAG3 receptor belongs to a family of immune-checkpoints expressed in T lymphocytes and other cells the immune system. It plays an important role as rheostat response. Focus on this potential therapeutic target cancer immunotherapy has been underscored after success immune-checkpoint blockade strategies clinical trials. showcases interest field autoimmunity several studies show that LAG3-targeting antibodies can also be used for treatment autoimmune diseases. In work we describe...