A5039064555- CAR-T cell therapy research
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Advanced Proteomics Techniques and Applications
- Cancer Research and Treatments
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Genomics and Phylogenetic Studies
- Animal Virus Infections Studies
- Genetics, Bioinformatics, and Biomedical Research
- Viral gastroenteritis research and epidemiology
- Ovarian cancer diagnosis and treatment
- Cancer Immunotherapy and Biomarkers
- Ubiquitin and proteasome pathways
- Colorectal and Anal Carcinomas
- Inflammasome and immune disorders
- Bioinformatics and Genomic Networks
- COVID-19 Clinical Research Studies
- interferon and immune responses
- Dermatological and COVID-19 studies
- Intraperitoneal and Appendiceal Malignancies
- Immune Response and Inflammation
- Machine Learning in Bioinformatics
Universidad de Navarra
2019-2025
Navarre Institute of Health Research
2019-2025
Clinica Universidad de Navarra
2025
Bipar
2021
Interleukin-12 (IL-12) gene transfer enhances the therapeutic potency of adoptive T cell therapies. We previously reported that transient engineering tumor-specific CD8 cells with IL-12 mRNA enhanced their systemic efficacy when delivered intratumorally. Here, we mix engineered mRNAs to express either single-chain (scIL-12) or an IL-18 decoy-resistant variant (DRIL18) is not functionally hampered by binding protein (IL-18BP). These mRNA-engineered mixtures are repeatedly injected into mouse...
Background BO-112 is a nanoplexed form of polyinosinic:polycytidylic acid that acting on toll-like receptor 3 (TLR3), melanoma differentiation-associated protein 5 (MDA5) and kinase RNA-activated (PKR) elicits rejection directly injected transplanted tumors, but has only modest efficacy against distant untreated tumors. Its clinical activity also been documented in early phase trials. The 5,6-dimethylxanthenone-4-acetic (DMXAA) stimulator interferon genes (STING) agonist shows comparable...
IL-12 is a potent cytokine for cancer immunotherapy. However, its systemic delivery as recombinant protein has shown unacceptable toxicity in the clinic. Currently, intratumoral injection of IL-12-encoding mRNA or DNA to avoid such side effects being evaluated clinical trials. In this study, we aimed improve strategy by further favoring tethering tumor. We generated vitro transcribed mRNAs encoding murine single-chain fused diabodies binding CSF1R and/or PD-L1. These targeted molecules are...
The resurgence of COVID-19 and the rise in severe outcomes emphasize need for reliable prognostic markers to guide patient care optimize ICU hospital resources. This study investigates potential nasopharyngeal swabs identify biomarkers that predict admission or death hospitalized patients. We analyzed exudates from 95 patients 2020 using high-plex RNA quantification on NanoString® nCounter platform. Comparative analysis identified four genes, with KLRB1 (Killer cell lectin like receptor B1)...
Peritoneal carcinomatosis is an advanced stage of cancer with very limited treatment options. Locoregional immunotherapy being evaluated as a way to improve efficacy and limit toxicity. This study assessed the cationic polymer/lipid-based transfection compound in delivering mRNA molecules intraperitoneally. Our investigation transfer luciferase murine models peritoneal revealed preferential expression omentum upon intraperitoneal administration complexed mRNAs. Macrophages were identified...
IL12-based local gene therapy of cancer constitutes an active area clinical research using plasmids, mRNAs, and viral vectors. To improve antitumor effects, we have experimentally tested the combination mRNA constructs encoding IL12 IL18. Moreover, used a form IL18 [decoy-resistant (DR-18)] which has preserved bioactivity but does not bind to binding protein decoy receptor. Both cytokines dramatically synergize induce IFNγ release from mouse splenocytes, and, if systemically cotransferred...
BO-112 is a poly I:C-based viral mimetic that exerts anti-tumor efficacy when intratumorally delivered in mouse models. Intratumoral synergizes mice with systemic anti-PD-1 mAbs and this combination has attained PD1-refractory melanoma patients. We sought to evaluate the of pre-surgically applied neoadjuvant settings have observed repeated intratumoral injections prior surgical excision primary tumor significantly reduced metastasis from orthotopically implanted 4T1-derived tumors...
Previous studies have shown that local delivery of tumor antigen-specific CD8+ T lymphocytes engineered to transiently express single-chain IL-12 mRNA is highly efficacious. Peritoneal dissemination cancer a frequent and often fatal patient condition usually diagnosed when the burden too large hence uncontrollable with current treatment options. In this study, we modeled intracavitary adoptive cell therapy OVA-specific OT-I cells electroporated treat B16-OVA PANC02-OVA spread in peritoneal...
Background Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to peritoneal cavity. In order restore antitumor immunity subverted by tumor cells this location, we evaluated intraperitoneal administrations modified vaccinia virus Ankara (MVA) engineered express single-chain interleukin 12 (scIL-12) increase immune responses. Methods MVA encoding scIL-12 (MVA.scIL-12) was against models based on engraftment cells. CD8-mediated responses, elucidated...
Background Lymphocytic choriomeningitis virus (LCMV) belongs to the Arenavirus family known for inducing strong cytotoxic T-cell responses in both mice and humans. LCMV has been engineered development of cancer immunotherapies, currently undergoing evaluation phase I/II clinical trials. Initial findings have demonstrated safety an exceptional ability activate expand tumor-specific T lymphocytes. Combination strategies maximize antitumor effectiveness LCMV-based immunotherapies are being...
Recombinant-modified vaccinia virus Ankara (rMVA) is known to elicit potent antitumor immune responses in preclinical models due its inherent ability activate the innate system and activation of adaptive mediated by expression tumor antigens costimulus-providing molecules, such as CD40L CD137L. Here, we evaluated different rMVA vectors peritoneal carcinomatosis (ID8.OVA-Vegf/GFP MC38). We compared expressing a antigen (OVA or gp70) either alone co-expressed with or/and In tumor-free mice,...
The Human Proteome Project (HPP) is leading the international effort to characterize human proteome. Although main goal of this project was first focused on detection missing proteins, a new challenge arose from need assign biological functions uncharacterized proteins and describe their implications in diseases. Not only with experimental evidence (uPE1 proteins) but also (uMPs) were objects study challenge, neXt-CP50. In work, we developed bioinformatic approach infer annotations for uPE1...
<div>Abstract<p>IL12-based local gene therapy of cancer constitutes an active area clinical research using plasmids, mRNAs, and viral vectors. To improve antitumor effects, we have experimentally tested the combination mRNA constructs encoding IL12 IL18. Moreover, used a form IL18 [decoy-resistant (DR-18)] which has preserved bioactivity but does not bind to binding protein decoy receptor. Both cytokines dramatically synergize induce IFNγ release from mouse splenocytes, and, if...
<div>Abstract<p>IL12-based local gene therapy of cancer constitutes an active area clinical research using plasmids, mRNAs, and viral vectors. To improve antitumor effects, we have experimentally tested the combination mRNA constructs encoding IL12 IL18. Moreover, used a form IL18 [decoy-resistant (DR-18)] which has preserved bioactivity but does not bind to binding protein decoy receptor. Both cytokines dramatically synergize induce IFNγ release from mouse splenocytes, and, if...
<p>Supplementary figures 1-8 and supplementary table 1</p>
<p>Supplementary figures 1-8 and supplementary table 1</p>
Abstract Peritoneal carcinomatosis is an advanced stage of cancer developed in the peritoneal cavity without effective treatment. In order to restore antitumor immunity subverted by tumor cells, we evaluated this study intraperitoneal administration vaccinia virus Ankara (MVA) genetically modified express proinflammatory cytokine single-chain interleukin 12. MVA encoding scIL-12 was models based on cells. The immune response ELISpot, flow cytometry, intravital microscopy, and depleting...
Abstract Local intratumoral NK cell activity is known to foster adaptive T cell-mediated immunity against cancer, that conceivably inhibited by the interactions of inhibitory receptor NKG2A with MHC class I molecule HLA-E in humans or Qa-1b mice. In this study, we found delivery cells significantly attains therapeutic effects only if co-injected anti-NKG2A and anti-Qa1b blocking monoclonal antibodies (mAb) two solid mouse tumors models. Such was contingent on endogenous CD8 type-1...
<h3>Background</h3> Interleukin-12 (IL-12) is a potent immunotherapeutic cytokine in mouse models which application as systemic agent the clinical setting hampered by IFNγ-dependent toxicity.<sup>1</sup> Engineering T cells with IL-12 highly efficacious models<sup>2</sup> but has resulted serious adverse events settings.<sup>3</sup> On other hand, IL-18 myeloid-derived that elicits IFN-γ expression on and NK lymphocytes.<sup>4</sup> are known to synergize terms of eliciting massive IFNγ...