Polyoxidonium ® Activates Cytotoxic Lymphocyte Responses Through Dendritic Cell Maturation: Clinical Effects in Breast Cancer

Immunotherapy, which is seen as a major tool for cancer treatment, requires, in some cases, the presence of several agents to maximize its effects. Adjuvants can enhance the effect of other agents. However, despite their long-time use, only a few adjuvants are licensed today, and their use in cancer treatment is rare. Azoximer bromide, marketed under the trade name Polyoxidonium® (PO), is a copolymer of N-oxidized 1,4-ethylenepiperazine and (N-carboxyethyl)-1,4-ethylene piperazinium bromide. It has been described as an immune adjuvant and immunomodulator that is clinically used with excellent tolerance. PO is used in the treatment and prophylaxis of diseases connected with damage to the immune system, and there is interest in testing it in antitumor therapy. We show here that PO treatment for 1 week induced positive pathological changes in 6 out of 20 patients with breast cancer, including complete response in a triple-negative patient. This correlated with an increased tumor CD4+ T-lymphocyte infiltration. The immune effects of PO are associated with myeloid cell activation, and little is known about the action of PO on lymphocyte lineages, such as natural killer (NK) and T cells. We reveal that PO increases T-cell proliferation in vitro without negative effects on any activation marker. PO does not affect dendritic cell (DC) viability and increases the expansion of immature DC (iDC) and mature DC (mDC) at 100 μg/ml, and it stimulates expression of several DC co-stimu...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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            Basel, 24 January 2020 – Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the Phase III IMvigor010 study evaluating Tecentriq® (atezolizumab) as an adjuvant (after surgery) monotherapy treatment did not meet its primary endpoint of disease-free survival (DFS) compared to observation in people with muscle-invasiv e urothelial cancer (MIUC). Safety for Tecentriq appeared consistent with the known safety profile of the medicine, and no new safety signals were identified.“Reducing the risk that muscle-invasive urothelial cancer will recur after surgery is ve...
Source: Roche Investor Update - Category: Pharmaceuticals Source Type: news
The Editor-in-Chief has retracted this article.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Contributors : Yuanzhang Fang ; Xinna ZhangSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusCurrent cancer immunotherapies are assumed to improve infiltration and cytotoxicity of immune cells in the tumor. However, tumor cells have developed a variety of resistance mechanisms to suppress the  MHC class I antigen presentation, and thereby impair the cytotoxicity of CD8+ T cells. Here, we identified Mal2 as a key player that mediates the turnover of the antigen-MHC-I complex and reduce the antigen presentation on tumor cells. Mal2 promotes the endocytosis of tumor antigen ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
Major differences in the results of two separate studies with addition of immunotherapy in triple-negative breast cancer are making this space more complicated than clear, according to Dr Kathy Miller.Medscape Oncology
Source: Medscape Hematology-Oncology Headlines - Category: Cancer & Oncology Tags: Hematology-Oncology Commentary Source Type: news
This study is the first to investigate the immunogenicity of LDHC using T cells from healthy individuals. LDHC-specific T cell responses were induced by in vitro stimulation with synthetic peptides, or by priming with autologous peptide-pulsed dendritic cells. We evaluated T cell activation by IFN- γ ELISpot and determined cytolytic activity of HLA-A*0201-restricted T cells in breast cancer cell co-cultures. In vitro T cell stimulation induced IFN-γ secretion in response to numerous LDHC-derived peptides. Analysis of HLA-A*0201 responses revealed a significant T cell activation after stimula tion with peptide p...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Publication date: Available online 10 January 2020Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Jamshid Gholizadeh Navashenaq, Parvin Zamani, Amin Reza Nikpoor, Jalil Tavakkol-Afshari, Mahmoud Reza JaafariAbstractMyeloid-derived suppressor cells (MDSCs) play a pivotal role in cancer. To overcome the problem of the MDSCs in the tumor microenvironment in this study, a combination of immunotherapy and chemotherapy was used. For this purpose, a liposomal formulation of P5 peptide and PEGylated liposomal doxorubicin (Doxil®) was utilized to treat mice bearing HER2+ tumor model. The results revealed th...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research
Abstract The great success of immunotherapy is paving the way for a new era in cancer treatment and is driving major improvements in the therapy of patients suffering from a range of solid tumors. However, the choice of the appropriate tumor antigens to be targeted with cancer vaccines and T-cell therapies is still a challenge. Most antigens targeted so far have been identified on the tumor bulk and are expressed on differentiated cancer cells. The discovery of a small population of cancer stem cells (CSC), which is refractory to most current therapies and responsible for the development of metastasis and recurren...
Source: Seminars in Immunology - Category: Allergy & Immunology Authors: Tags: Semin Immunol Source Type: research
In conclusion, our analysis identifies genes signatures with potential to recognize immune activated ovarian and basal-like breast cancers with favorable prognosis and with a remarkable predictive capacity in tumors with low mutational burden. The presented results led to a hypothesis being formulated, but prospective clinical studies are needed to support a potential clinical application.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
AbstractThe overall aim of this prospective study was to delineate the role of monocytic myeloid-derived suppressor cells (Mo-MDSCs) in patients with metastatic breast cancer (MBC). MDSCs are a heterogeneous group of immunosuppressive cells often enriched in different malignancies which hold prognostic and predictive value for clinical outcomes. Here, we assessed the clinical significance of Mo-MDSCs in 54 patients with de novo or distant recurrent MBC. We show that high levels of Mo-MDSCs significantly correlated with de novo MBC (metastatic disease at initial diagnosis), estrogen receptor (ER) negativity, and liver- and ...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
In this study, we evaluated the specification of a designed immunotoxin formed by EPHA2-specific scfv linked with PE38KDEL on EPHA2-overexpressing breast cancer cell line. This new scfv-based recombinant immunotoxin was studied in terms of features such as binding potency, cytotoxicity effects, apoptosis induction ability, and internalization. The flow cytometry results showed that the immunotoxin can significantly (approximately 99%) bind to EPHA2-overexpressing breast cancer cell line (MDA-MB-231) in a low concentration (2.5 ng/ul) while cannot significantly bind to the normal cell line (HEK-293) or even EPHA2-very low e...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
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