Search results for "Immunotherapy."
showing 10 items of 819 documents
T-cell Receptor Therapy Targeting Mutant Capicua Transcriptional Repressor in Experimental Gliomas
2021
Abstract Purpose: Gliomas are intrinsic brain tumors with a high degree of constitutive and acquired resistance to standard therapeutic modalities such as radiotherapy and alkylating chemotherapy. Glioma subtypes are recognized by characteristic mutations. Some of these characteristic mutations have shown to generate immunogenic neoepitopes suitable for targeted immunotherapy. Experimental Design: Using peptide-based ELISpot assays, we screened for potential recurrent glioma neoepitopes in MHC-humanized mice. Following vaccination, droplet-based single-cell T-cell receptor (TCR) sequencing from established T-cell lines was applied for neoepitope-specific TCR discovery. Efficacy of intravent…
Long-term freedom from recurrence in 2 stage IV melanoma patients following vaccination with tyrosinase peptides.
2002
We report here on 2 patients who received adjuvant vaccination with an HLA-A2- or HLA-A24-restricted tyrosinase peptide, respectively, and GM-CSF for frequently relapsing stage IV melanoma. Following resection of metastases and irradiation of brain metastases in 1 patient, both patients were without evidence of disease when receiving the first vaccination. While the patients had had 9 and 12, respectively, mostly s.c., relapses during the 3 years before vaccination, they experienced freedom from relapse for more than 2 years after vaccination. We found a T-cell response to the vaccine peptide in both patients in the peripheral blood by ex vivo IFN-gamma ELISPOT assay. The T-cell population …
CD83+ human dendritic cells transfected with tumor peptide cDNA by electroporation induce specific T-cell responses: A potential tool for gene immuno…
2000
Dendritic cells (DC) are the most potent immunostimulatory cells, with the capacity to induce primary T-cell responses. Functional autologous DC can be generated from fetal calf serum-free peripheral blood mononuclear cells in the presence of interleukin-4 and granulocyte-macrophage colony-stimulating factor and are stimulated with a defined cytokine cocktail for terminal maturation. We were able to establish a nonviral transfection protocol for these DC by electroporation. Using enhanced green fluorescent protein as a reporter gene, we achieved transfection efficiencies of up to 10%. FACScan analyses revealed a stable phenotype, and the expression of major histocompatibility complex class …
Abstract 4740: Doxorubicin eliminates tumor-induced myeloid-derived suppressor cells and enhances T-helper lymphocyte-based immunotherapy in a murine…
2013
Abstract Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population of cells equipped with the ability to inhibit T lymphocyte-mediated immune responses. A significant increase in the number of MDSC has been reported in the blood, secondary lymphoid organs and tumor beds in tumor-bearing animals and in patients with many types of cancers. MDSC frequency correlates with the disease stage and prognosis. These cells impair CD8+ cytotoxic T lymphocyte (CTL)-mediated anti-tumor immunity by different overlapping mechanisms such as reactive oxygen species or immunosuppressive cytokine production. Importantly, MDSC elimination or inactivation substantially enhances the efficiency …
Humoral immune responses of cancer patients against “Cancer-Testis” antigen NY-ESO-1: Correlation with clinical events
1999
Humoral immune responses against the "Cancer-Testis" (CT) antigen NY-ESO-1 are frequently observed in patients with NY-ESO-1 expressing tumors. This is in contrast to other known tumor antigens (TA) defined by antibody or cytotoxic T cell (CTL) reactivity, i.e., MAGE-1, MAGE-3, SSX2, Melan A, and tyrosinase. No NY-ESO-1 antibody has been detected in healthy controls and patients with NY-ESO-1 negative tumors. In this study, we have assessed the NY-ESO-1 serum antibody response in patients with NY-ESO-1 positive tumors of different histological types and stages using Western blotting and an ELISA. Of the 12 patients analyzed, 10 had demonstrable NY-ESO-1 antibodies at the start of the study.…
Abstract B041: A novel nanoparticular formulated tetravalent RNA cancer vaccine for treatment of patients with malignant melanoma
2016
Abstract Immunotherapeutic approaches have evolved as promising and valid alternatives to available conventional cancer treatments. Amongst others, vaccination with tumor antigen-encoding RNAs by local administration is currently successfully employed in various clinical trials. To allow for a more efficient targeting of antigen-presenting cells (APCs) we have developed a novel RNA immunotherapeutic for systemic application based on a fixed set of four liposome complexed RNA drug products (RNA(LIP)) each encoding one shared melanoma-associated antigen. Similar to other liposomal drugs, the four injectable RNA(LIP) products constituting the investigational medicinal product will be prepared …
A novel predictive biomarker of immunotherapy response in metastatic renal cell carcinoma (mRCC): The lymphocyte microRNA expression profile.
2019
e16109 Background: Predicting which patient with metastatic renal cell carcinoma (mRCC) will benefit from immune checkpoints inhibitors (ICPIs) still remain an issue. Biological factors particular to certain individuals have a clear effect on variation in response. Emerging evidence suggests that small non-coding RNA, such as microRNAs (miRNAs), are critical modulators of numerous cellular processes, including immune surveillance. The main aim of this study was to analyze the lymphocyte miRNA expression profile in mRCC patients and dynamic changes after the treatment with ICPI, in order to investigate the molecular mechanisms and signaling pathways involved in ICPI response and their poten…
Abstract B157: OX40 expression in tumor-associated Tregs as a potential prognostic biomarker and immunotherapeutic target in ovarian cancer
2016
Abstract Background - Treatment of ovarian cancer remains very challenging, with 80-85% of the cases still dying after relapse to standard chemotherapy, and alternative treatments are urgently needed. Expansion of regulatory T cells (Tregs) is considered the major factor limiting spontaneous immune responses to ovarian cancer. Agonist antibodies against the co-stimulatory receptor OX40 have recently demonstrated to abrogate Treg functions and are under clinical evaluation. We thus studied whether OX40 constituted a valid target of ovarian cancer-associated Tregs. Methods -Treg immunophenotypic analyses were performed by flow cytometry in ascites and ovarian cancer specimens and studied in a…
In the literature: August 2020.
2020
Immune checkpoint inhibitors (ICI) have become a key component of therapy for several solid tumours. In patients diagnosed with advanced clear cell renal cell carcinoma (ccRCC), immunotherapy has always been considered as a treatment option, and anti-PD-1-based therapies are approved in both the frontline and refractory settings. Response to PD-1 blockade has been associated with numerous tumour-intrinsic and microenvironment features. Genetic characterisation of ccRCC has significantly contributed to the knowledge of tumour biology and the mechanisms of disease progression, but the interplay of genomic alterations with patterns of immune infiltration in response to PD-1 blockade remains un…
7 Evolution of cross-resistance to CD8+ T cells in the course of BRAF and MEK inhibitor treatment in BRAFV600E melanoma
2018
Introduction The BRAFV600 mutation, expressed in approximately 50% of melanomas, mediates constitutive activation of the BRAF-MEK-ERK in the MAPK signalling pathway and therefore tumour proliferation. Rapid and high rate of clinical responses can be achieved by targeting this axis using BRAF V600 inhibitor (BRAFi) as single therapy or the combination of BRAFi and MEKi (BRAFi/MEKi). But still disease progresses in the majority of treated patients due to acquired resistance in tumour cells. Combining targeted therapy with immunotherapy is proposed to improve the long-term outcomes of patients. However, to which extent BRAFi may affect melanoma immunogenicity over time remains largely unknown.…