Development of Effective Cancer Vaccine Using Targeting System of Antigen Protein to APCs.

PURPOSE: To develop a novel cancer vaccine using the targeting system of antigen protein to antigen-presenting cells (APCs) for efficient and safe cancer therapy. METHODS: The novel delivery system was constructed with antigen protein, benzalkonium chloride (BK), and γ-polyglutamic acid (γ-PGA), using ovalbumin (OVA) as a model antigen protein and evaluating its immune induction effects and utilities for cancer vaccine. RESULTS: BK and γ-PGA enabled encapsulation of OVA and formed stable anionic particles at nanoscale, OVA/BK/γ-PGA complex. Complex was taken up by dendritic cell line DC2.4 cells efficiently. We subcutaneously administered the complex to mice and examined induction of IgGs. The complex induced not only Th2-type immunoglobulins but also Th1-type immunoglobulins. OVA/BK/γ-PGA complex inhibited tumor growth of E.G7 cells expressing OVA regularly; administered OVA/BK/γ-PGA complex completely rejected tumor cells. CONCLUSION: The novel vaccine could be platform technology for a cancer vaccine

Engagement of different Fc-gamma receptors in phagocytosis of immune complexes containing antibodies to mutated human chorionic gonadotropin β chain (hCG-beta) and native hCG molecule

The aim of this study was to investigate the role of Fcγ receprors (FcγR) in vitro, in phagocytosis of hormone-antibody complexes formed after immunization with the mutant hCGβ(R68E). Native, FITC labeled hCG was added to the sera from mutant hCGβ(R68E) immunized rabbits. The suspensions of phagocytic cells were selectively incubated with monoclonal antibodies to FcγRI, FcγRII, FcγRIII and the complement receptor 3 in order to block their functions and phagocytosis was visualized by flow cytometry. We show that the phagocytosis of immune complexes containing anti-hCGβ(R68E) sera of rabbits and native hCG molecules by monocytes and neutrophils is mediated by FcγRI(CD64) and FcγRIII(CD16) respectively in cooperation with the complement receptor 3 (CR3)

Study to evaluate the immunomodulatory effects of radiofrequency ablation compared to surgical resection for liver cancer

Introduction: Hepatic cancer is a highly lethal tumour with increasing worldwide incidence. These tumours are characterized by the proliferation of malignant cells, generalised immunosuppression and chronic inflammation marked with an increase in inflammatory markers as a neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and overexpression of CD4+CD39+ on T lymphocytes. The studies have outlined immunomodulatory changes in liver cancer patients as the plausible explanation for the better survival. The aim of this pilot study was understand the possible immunomodulatory effect of radiofrequency (RF) energy and liver resection (non-radiofrequency based devices; non-RF device) in relation to NLR, PLR and expression of CD4+CD39+ T lymphocytes and compare the magnitude of these changes. Material and Methods: In the present study, 17 patients with hepatic cancer were prospectively divided into treatment groups radiofrequency ablation (RFA group) and Liver resection using non-RF devices (LR group). A blood sample was collected from each patient, one month before and after the procedure and compared with the blood samples of age-matched healthy volunteers for group wise comparison. The Mann-Whitney U test, Mc Nemar test and Wilcoxon rank test were used for statistical comparisons as appropriate. Results: A decrease in NLR was reported after RFA from 4.7±3.3 to 3.8±1.8 (P=0.283), in contrary to an increase from 3.5±2.8 to 4.5±3.2 (P=0.183) in LR group. Likewise, a decrease was discerned in PLR following RFA from 140.5±79.5 to 137±69.2 respectively (P=0.386) and increase in the LR group from 116±42.2 to 120.8±29 respectively (P=0.391). A significant decrease in CD4+CD39+ lymphocytes from 55.8±13.8 to 24.6±21.1 (P=0.03) was observed in RFA group whilst a significant increase was reported in LR group from 47.6±8.8 to 55.7±33.2 (P=0.38). Conclusion: Studies have shown that decrease in the NLR, PLR and expression of CD4+CD39+ on T lymphocytes as the marker of better survival in hepatic cancer patients and our findings have confirmed that these changes can be induced following application of RF energy. Moreover, this could be the explanation of better survival observed in different studies using RFA or other RF-based devices in comparison to non-RF based liver resection techniques. However, further larger studies are needed to confirm these findings

Immunomodulatory changes following isolated RF ablation in colorectal liver metastases: a case report

Background: Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related deaths in developed countries. The liver is the most prevalent site of metastasis from CRC. Currently, the gold-standard treatment for colorectal liver metastases (CLMs) is surgical resection. However, depending on the pattern of the disease, a significant number of patients may require different approaches alone or in combination with surgery, including thermal ablation (radiofrequency (RFA) or microwave (MWA) ablation) or transarterial liver-directed therapies, although the latter is not yet part of the standard treatment for CRC liver metastases. Methods and Results: We present the case of a 63-yearold man with bilobar CLM who was treated with transarterial embolization (TAE) and RFA followed by chemotherapy. A post-RFA study of immune parameters revealed the downregulation of CD39 expression in the circulating CD4+ T cell population and a reduction of the serum levels of cytokines IL-10, TGF-β, IFN-gamma and IL-17, which positively correlated with the diminished serum level of gamma-glutamyl transferase (GGT) and the subdued inflammatory markers: the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR). Later, the patient underwent chemotherapy. Liver failure developed within two years and nine months following tumour ablation, leading to the death of the patient. Conclusions: However, the denial of adjuvant chemotherapy by the patient gave us the opportunity to assess the immunomodulatory changes following RFA in the absence of any other therapeutic modalities

Fc gamma receptor expression on splenic macrophages in adult immune thrombocytopenia

Splenic macrophages play a key role in immune thrombocytopenia (ITP) pathogenesis by clearing opsonized platelets. Fc receptors (FcR) participate in this phenomenon, but their expression on splenic macrophages and their modulation by treatment have scarcely been studied in human ITP. We aimed to compare the phenotype and function of splenic macrophages between six controls and 24 ITP patients and between ITP patients according to the treatments they received prior to splenectomy. CD86, human leucocyte antigen D-related (HLA-DR) and FcR expression were measured by flow cytometry on splenic macrophages. The major FcR polymorphisms were determined and splenic macrophage function was assessed by a phagocytosis assay. The expression of the activation markers CD86 and HLA-DR was higher on splenic macrophages during ITP compared to controls. While the expression of FcR was not different between ITP and controls, the phagocytic function of splenic macrophages was reduced in ITP patients treated with intravenous immunoglobulin (IVIg) within the 2weeks prior to splenectomy. The FCGR3A (158V/F) polymorphism, known to increase the affinity of FcRIII to IgG, was over-represented in ITP patients. Thus, these are the first results arguing for the fact that the therapeutic use of IVIg during human chronic ITP does not modulate FcR expression on splenic macrophages but decreases their phagocytic capabilitie

Fcγ receptor expression on splenic macrophages in adult immune thrombocytopenia

Splenic macrophages play a key role in immune thrombocytopenia (ITP) pathogenesis by clearing opsonized platelets. Fcγ receptors (FcγR) participate in this phenomenon, but their expression on splenic macrophages and their modulation by treatment have scarcely been studied in human ITP. We aimed to compare the phenotype and function of splenic macrophages between six controls and 24 ITP patients and between ITP patients according to the treatments they received prior to splenectomy. CD86, human leucocyte antigen D-related (HLA-DR) and FcγR expression were measured by flow cytometry on splenic macrophages. The major FcγR polymorphisms were determined and splenic macrophage function was assessed by a phagocytosis assay. The expression of the activation markers CD86 and HLA-DR was higher on splenic macrophages during ITP compared to controls. While the expression of FcγR was not different between ITP and controls, the phagocytic function of splenic macrophages was reduced in ITP patients treated with intravenous immunoglobulin (IVIg) within the 2 weeks prior to splenectomy. The FCGR3A (158V/F) polymorphism, known to increase the affinity of FcγRIII to IgG, was over-represented in ITP patients. Thus, these are the first results arguing for the fact that the therapeutic use of IVIg during human chronic ITP does not modulate FcγR expression on splenic macrophages but decreases their phagocytic capabilities