Search results for " IMMUNOTHERAPY"

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 …

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 …

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…

Immunological aspects of heat shock protein functions and their significance in the development of cancer vaccines

2022

The primary function of intracellular heat shock proteins (HSPs) is to protect the cell by suppressing the effects of various stress factors by either refolding misfolded proteins or blocking apoptosis. After neoplastic transformation, cells overexpress HSPs, which act as factors promoting the neoplastic process by stabilizing proteins responsible for carcinogenesis, however, HSPs can be released into the extracellular environment where they act as important modulators of the immune response. In a tumor microenvironment, extracellular HSPs are able to induce a pro- or anti-neoplastic response, using various mechanisms of affecting immune cells, The study of the role of extracellular HSPs in…

Overall survival at 5 years of follow-up in a phase III trial comparing ipilimumab 10 mg/kg with 3 mg/kg in patients with advanced melanoma

2020

BackgroundWe have previously reported significantly longer overall survival (OS) with ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with advanced melanoma, with higher incidences of adverse events (AEs) at 10 mg/kg. This follow-up analysis reports a 5-year update of OS and safety.MethodsThis randomized, multicenter, double-blind, phase III trial included patients with untreated or previously treated unresectable stage III or IV melanoma. Patients were randomly assigned (1:1) to ipilimumab 10 mg/kg or 3 mg/kg every 3 weeks for 4 doses. The primary end point was OS.ResultsAt a minimum follow-up of 61 months, median OS was 15.7 months (95% CI 11.6 to 17.8) at 10 mg/kg and 11.5 mont…

Dendritic cell-tumor cell hybrids and immunotherapy: what's next?

2011

Dendritic cells (DC) are professional antigen-presenting cells currently being used as a cellular adjuvant in cancer immunotherapy strategies. Unfortunately, DC-based vaccines have not demonstrated spectacular clinical results. DC loading with tumor antigens and DC differentiation and activation still require optimization. An alternative technique for providing antigens to DC consists of the direct fusion of dendritic cells with tumor cells. These resulting hybrid cells may express both major histocompatibility complex (MHC) class I and II molecules associated with tumor antigens and the appropriate co-stimulatory molecules required for T-cell activation. Initially tested in animal models, …

mTOR Inhibition Improves Antitumor Effects of Vaccination with Antigen-Encoding RNA

2013

Abstract Vaccination with in vitro transcribed RNA encoding tumor antigens is an emerging approach in cancer immunotherapy. Attempting to further improve RNA vaccine efficacy, we have explored combining RNA with immunomodulators such as rapamycin. Rapamycin, the inhibitor of mTOR, was used originally for immunosuppression. Recent reports in mouse systems, however, suggest that mTOR inhibition may enhance the formation and differentiation of the memory CD8+ T-cell pool. Because memory T-cell formation is critical to the outcome of vaccination aproaches, we studied the impact of rapamycin on the in vivo primed RNA vaccine-induced immune response using the chicken ovalbumin-expressing B16 mela…

Heat Shock Protein Vaccines Against Cancer

1993

Vaccination of mice with heat shock proteins (HSPs) derived from a tumor makes the mice resistant to the tumor from which the HSP was obtained. This phenomenon has been demonstrated with three HSPs--gp96, hsp90, and hsp70. Vaccination with HSPs also elicits antigen-specific cytotoxic T lymphocytes (CTLs). The specific immunogenicity of HSPs derives apparently, not from the HSPs per se, but from the peptides bound to them. These observations provide the basis for a new generation of vaccines against cancer. The HSP-based cancer vaccines circumvent two of the most intractable hurdles to cancer immunotherapy. One of them is the possibility that human cancers, like cancers of experimental anima…

Addressing tumour tolerance to improve cancer immunotherapy

2010

Immune Control in Hepatocellular Carcinoma Development and Progression: Role of Stromal Cells

2014

Immune control of hepatocellular carcinoma (HCC) is executed by effector immune cells, which efficiently eliminate malignant transformed cells. However, progression of HCC clearly documents failure of tumor immune control, which led to the concept of immune subversion by the tumor environment. Particularly tumor-associated stromal cells cooperate within an inflammatory network, which is responsible for immune privilege. The stromal cell composition matures during tumor growth and is derived from surrounding noncancerous tissue or from circulating cells recruited to the tumor site. Therefore, immunosuppressive stromal cells represent heterogeneous cell lineages, including myeloid cells, lymp…