A5072852574- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Viral Infections and Vectors
- Mosquito-borne diseases and control
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Cancer Research and Treatments
- Immune cells in cancer
- Monoclonal and Polyclonal Antibodies Research
- Viral Infections and Outbreaks Research
- interferon and immune responses
- Chemokine receptors and signaling
- Gastric Cancer Management and Outcomes
- Advanced Drug Delivery Systems
- Cancer Cells and Metastasis
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cancer, Stress, Anesthesia, and Immune Response
- Nanoparticle-Based Drug Delivery
- Esophageal Cancer Research and Treatment
- vaccines and immunoinformatics approaches
- Cytokine Signaling Pathways and Interactions
- Cancer, Hypoxia, and Metabolism
Memorial Sloan Kettering Cancer Center
2022-2025
Kettering University
2024-2025
Parker Institute for Cancer Immunotherapy
2023-2025
Universidad de Navarra
2016-2023
Navarre Institute of Health Research
2016-2023
Centro de Investigación Biomédica en Red de Cáncer
2018-2021
Clinica Universidad de Navarra
2016-2021
Public neoantigens (NeoAgs) represent an elite class of shared cancer-specific epitopes derived from recurrently mutated driver genes. Here we describe a high-throughput platform combining single-cell transcriptomic and T cell receptor (TCR) sequencing to establish whether mutant PIK3CA, among the most frequently genomically altered oncogenes, generates immunogenic public NeoAg. Using this strategy, developed panel TCRs that recognize endogenously processed neopeptide encompassing common...
Poly I:C is a powerful immune adjuvant as result of its agonist activities on TLR-3, MDA5 and RIG-I. BO-112 nanoplexed formulation complexed with polyethylenimine that causes tumor cell apoptosis showing immunogenic death features which upon intratumoral release results in more prominent infiltration by T lymphocytes. Intratumoral treatment subcutaneous tumors derived from MC38, 4 T1 B16-F10 leads to remarkable local disease control dependent type-1 interferon gamma-interferon. Some degree...
Abstract Radiotherapy can be synergistically combined with immunotherapy in mouse models, extending its efficacious effects outside of the irradiated field (abscopal effects). We previously reported that a regimen encompassing local radiotherapy combination anti-CD137 plus anti–PD-1 mAbs achieves potent abscopal against syngeneic transplanted murine tumors up to certain tumor size. Knowing TGFβ expression or activation increases tissues, we tested whether blockade may further enhance...
Interleukin-8 (CXCL8) produced in the tumor microenvironment correlates with poor response to checkpoint inhibitors and is known chemoattract activate immunosuppressive myeloid leukocytes. In human cancer, IL8 mRNA levels correlate IL1B TNF transcripts. Both cytokines induced IL-8 functional expression from a broad variety of cancer cell lines, primary colon carcinoma organoids, fresh explants. Although absent mouse genome, similar murine axis which TNFα IL-1β upregulate CXCL1 CXCL2 cells...
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...
Abstract T cell-based immunotherapies hold promise in treating cancer by leveraging the immune system’s recognition of cancer-specific antigens 1 . However, their efficacy is limited tumours with few somatic mutations and substantial intratumoural heterogeneity 2–4 Here we introduce a previously uncharacterized class tumour-wide public neoantigens originating from RNA splicing aberrations diverse types. We identified cell receptor clones capable recognizing targeting derived aberrant GNAS...
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 CD137 (4-1BB; TNFSR9) is an activation-induced surface receptor that through costimulation effects provide antigen-primed T cells with augmented survival, proliferation and effector functions as well metabolic advantages. These immunobiological mechanisms are being utilised for cancer immunotherapy agonist CD137-binding crosslinking-inducing agents elicit intracellular signaling. In this study, side-by-side comparisons show provision of in-cis regard to the TCR-CD3-ligating cell...
Abstract Neoantigens (NeoAgs) are a critical class of human cancer rejection antigens. The vast majority arise from random passenger mutations unique to single individual, which limits the systematic study molecular basis NeoAg immunogenicity in patients. In contrast, “public” clonally conserved epitopes derived recurrently mutated driver genes that shared among this study, we developed research platform perform comprehensive structural, biophysical, genetic, and immunogenic analysis family...
Abstract A major roadblock preventing durable responses to CD8+ T cell-based immunotherapies in melanoma and other solid cancers is loss or downregulation of human leukocyte antigen class I (HLA-I) on tumor cells. We hypothesized this immune escape mechanism might be overcome by tumor-reactive cytotoxic CD4+ cells which can directly engage that express HLA-II. Unlike HLA-I, the molecular mechanisms governing response resistance HLA-II presentation have previously not been studied a...
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...
Article19 November 2019Open Access Source DataTransparent process Repurposing the yellow fever vaccine for intratumoral immunotherapy Maria Angela Aznar Corresponding Author [email protected] orcid.org/0000-0002-7970-1672 Center Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain Search more papers by this author Carmen Molina Alvaro Teijeira CIBERONC, Madrid, Instituto de investigación Navarra (IDISNA), Inmaculada Rodriguez Arantza Azpilikueta Saray Garasa Alfonso R...
Activation-induced cell death (AICD) is a complex immunoregulatory mechanism that causes the demise of fraction T-lymphocytes upon antigen-driven activation.In present study we investigated direct role TNF in AICD CD8 T lymphocytes.Methods: Human peripheral mononuclear cells were isolated from healthy donors and fresh tumor-infiltrating lymphocytes obtained cancer patients undergoing surgery.T activated with anti-CD3/CD28 mAbs or pool virus peptides, combination clinicalgrade blocking...