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H. polygyrus: B7-independence of the secondary type 2 response.

The gastrointestinal nematode parasite, Heligmosomoides polygyrus, has been used extensively in experimental studies of host immunity. The pronounced type 2 primary immune response to H. polygyrus is associated with elevated CD4+, TCR-alpha/beta + T cell IL-4 production and elevated serum IgE levels that are blocked by inhibiting CD28/ CTLA4-B7 interactions following in vivo administration of the chimeric fusion protein, CTLA4Ig. In the present study, we have examined the in vivo effects of blocking CTLA4Ig ligands on the secondary type 2 mucosal host protective immune response to this parasit

Toxic shock syndrome toxin-1-induced death is prevented by CTLA4Ig.

Lethal toxic shock syndrome (TSS) results from the MHC class II presentation of bacterial superantigens, most commonly toxic shock syndrome-1 (TSST-1), to specific TCR Vbeta-bearing T cells. This superantigen-induced stimulation of whole T cell subsets leads to the exuberant cytokine production that in turn causes the shock syndrome. Since T cell activation and cytokine production are known to be dependent upon costimulatory signals, we reasoned that interfering with costimulation could effect TSS outcome. To test that hypothesis, we evaluated the effect of CTLA4Ig, a fusion protein known to b

Biomarker-driven management strategies for peripheral T cell lymphoma.

Peripheral T cell lymphomas are heterogeneous diseases which remain treatment challenges. Recent advances in molecular and genomic profiling have provided unprecedented insight into disease pathogenesis driven by distinct cells of origins and molecular pathways. The discovery and clinical application of molecular biomarkers in PTCL subtypes has the potential to transform personalized care for patients with PTCL in diagnosis, prognosis, and therapy. Targeting CD30+ PTCL with the antibody-drug conjugate brentuximab vedotin in the relapsed setting and in combination with chemotherapy in the front

Characterising the phenotypic evolution of circulating tumour cells during treatment.

Real-time monitoring of cancer cells' phenotypic evolution during therapy can provide vital tumour biology information for treatment management. Circulating tumour cell (CTC) analysis has emerged as a useful monitoring tool, but its routine usage is restricted by either limited multiplexing capability or sensitivity. Here, we demonstrate the use of antibody-conjugated and Raman reporter-coated gold nanoparticles for simultaneous labelling and monitoring of multiple CTC surface markers (named as "cell signature"), without the need for isolating individual CTCs. We observe cell heterogeneity and

Mesenchymal stem cells alleviate experimental autoimmune cholangitis through immunosuppression and cytoprotective function mediated by galectin-9.

BACKGROUND: Mesenchymal stem cells (MSCs) play an anti-inflammatory role by secreting certain bioactive molecules to exert their therapeutic effects for disease treatment. However, the underlying mechanism of MSCs in chronic autoimmune liver diseases-primary biliary cholangitis (PBC), for example-remains to be elucidated. METHODS: Human umbilical cord-derived MSCs (UC-MSCs) were injected intravenously into 2-octynoic acid coupled to bovine serum albumin (2OA-BSA)-induced autoimmune cholangitis mice. Serum levels of biomarkers and autoantibodies, histologic changes in the liver, diverse CD4+ T

[Therapeutic monoclonal antibodies in onco-hematology].

Rituximab, a chimeric monoclonal anti-CD20 antibody, was introduced into clinical practice in 1997, and has proven to be highly effective in the treatment of B-lymphoproliferative disorders and autoimmune diseases. Despite such success, in vivo mechanisms of action of anti-CD20 have only recently began to be unraveled, pointing to the crucial role of antibody-dependent cellular cytotoxicity response mediated through Fcg receptor signalling. Better understanding of pharmacokinetics and factors influencing individual exposure mediated through anti-CD20 will allow to engineer these molecules to i

Effect of anti-CD134L mAb and CTLA4Ig on ConA-induced proliferation, Th cytokine secretion, and anti-dsDNA antibody production in spleen cells from lupus-prone BXSB mice.

We sought to evaluate the effects of combined downregulation of CD134 and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) on the autoimmune process of lupus. Concanavalin A (ConA)-induced proliferation, T helper cell cytokine secretion, and anti-double stranded DNA (dsDNA) antibody production were measured in cultures of splenic lymphocytes derived from lupus-prone BXSB mice. Splenocytes from six prednisone-treated and six untreated male lupus-prone BXSB mice, as well as from six syngeneically normal C57BL/6 male mice, were stimulated with ConA. BXSB splenocytes from untreated mice were ex

Characteristics of inflammatory cells in spontaneous autoimmune thyroiditis of NOD.H-2h4 mice.

Thyroid lesions develop in most NOD.H-2h4 mice 6 weeks after they are given 0.05% NaI in drinking water. B cells are required for spontaneous autoimmune thyroiditis (SAT) development, and anti-thyroglobulin autoantibody levels correlate with SAT severity. Immunohistochemical staining of thyroids obtained 2-10 weeks after administration of NaI water suggested that CD4+ T cells initially infiltrated the thryoid, followed by CD8+ T cells and B cells. Intrathyroidal CD4+ T cells are more numerous than CD8+ T cells. CD4+ T cells and B cells form aggregates in the thyroid, while CD8+ T cells are sca

Retrospective analysis of the preparation and application of immunotherapy in cancer treatment (Review).

Monoclonal antibody technology plays a vital role in biomedical and immunotherapy, which greatly promotes the study of the structure and function of genes and proteins. To date, monoclonal antibodies have gone through four stages: murine monoclonal antibody, chimeric monoclonal antibody, humanised monoclonal antibody and fully human monoclonal antibody; thousands of monoclonal antibodies have been used in the fields of biology and medicine, playing a special role in the pathogenesis, diagnosis and treatment of disease. In this review, we compare the advantages and disadvantages of hybridoma te

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… Chemo-immunoconjugate The cytotoxic agent can conjugate with antitumour mAbs to form chemo-immunoconjugate, which can bind to the surface of antigen-positive tumour cells through the guidance of mAbs, inducing the internalisation of the conjugates ( 200 ). … As early as the beginning of the 1980s, Mew et al started studying PIT in vitro and in vivo , indicating that photo-immunoconjugates show higher selectivity to tumour tissues than photosensitisers or mAbs alone ( 233 , 234 ). …

Plasmablastic Lymphoma: Case Report of Prolonged Survival of an Advanced Human Immunodeficiency Patient and Literature Review.

Clinical Practice Points. Plasmablastic lymphoma (PBL) is a rare and highly aggressive variant of diffuse large B cell lymphoma with median survival of advanced stage patients varying between 6 and 15 months in previous reports. We report here a human immunodeficiency virus-infected patient surviving over 12 years following treatment for advanced PBL with EPOCH chemotherapy and intrathecal therapy. This case highlights the potential for improved survival in PBL with intensive chemotherapy. Further, literature review suggests promising prospects utilizing novel targeted therapies to increase th

Survival analysis of patients with Hodgkin lymphoma who failed high dose chemotherapy and autologous stem cell transplant.

Hodgkin lymphoma (HL) patients failing after high dose chemotherapy (HDC) and auto-SCT have a poor outcome. Some patients may still benefit from further treatments. From 1996 to 2016, 137 HL patients (39.5%) out of 347 transplanted experienced post auto-SCT failure. Males/female 61%:39%, median age at auto-SCT 23.4 years and median follow-up 55.6 months (9-153). Type of failure was progressive (46%), relapsed (35%) or persistent disease/refractory disease (19%). Median overall survival (OS) from the time of failure is 20 months; 35 patients (25.5%) are alive. One hundred and four patients rece

Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project.

PURPOSE: In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored. PATIENTS AND METHODS: In this phase II study, patients with MF or SS with negligible to 100% CD30 expression levels were treated with brentuximab vedotin (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The

Immunoliposome encapsulation increases cytotoxic activity and selectivity of curcumin and resveratrol against HER2 overexpressing human breast cancer cells.

Natural compounds have been studied as a source of countless bioactive compounds with diverse activities. Among them, many dietary phytochemicals have been thoroughly studied for their cytotoxic or apoptotic effects in several cellular models in order to explain their anticancer capacity. Curcumin and resveratrol are two natural compounds with a large body of evidence showing their cytotoxic activity against a wide variety of cancer cells; however, their poor absorption, bioavailability, and low selectivity have limited their clinical use. With the aim of improving bioavailability and selectiv

Infiltrating cellular pattern in kidney graft biopsies translates into forkhead box protein 3 up-regulation and p16INK4α senescence protein down-regulation in patients treated with belatacept compared to cyclosporin A.

Renal allograft survival is related directly to cell senescence. In the transplantation scenario many cellular events - participating as immunological and non-immunological factors - could contribute to accelerate this biological process, responsible for the ultimate fate of the graft. Mechanisms concerned in tolerance versus rejection are paramount in this outcome. For this reason, immunosuppressive treatment constitutes an extremely important decision to prevent organ dysfunction and, finally, graft loss. This study was conducted to document the proportion of CD4(+) /interleukin (IL)-17A(+)

Incidence of influenza-like illness into a cohort of patients affected by chronic inflammatory rheumatism and treated with biological agents.

This study aimed to evaluate the incidence of influenza-like illness (ILI), from October 2009 to May 2010, in a group of patients suffering from chronic inflammatory rheumatism and treated with biological therapies. At the end of 2009-2010 influenza season, 159 patients under biological therapies answered to a questionnaire distributed 8 months before and were deeply interviewed. The group included 69 men and 90 women (mean age 47.6); forty-nine suffering from rheumatoid arthritis, 61 with psoriatic arthritis, 32 with ankylosing spondylitis and 17 with other spondyloarthritis; 146 patients wer

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) can regulate dendritic cell-induced activation and cytotoxicity of CD8(+) T cells independently of CD4(+) T cell help.

The mechanisms that regulate the strength and duration of CD8(+) cytotoxic T cell activity determine the effectiveness of an antitumor immune response. To better understand the antitumor effects of anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody treatment, we analyzed the effect of CTLA-4 signaling on CD8(+) T cells in vitro and in vivo. In vitro, cross-linking of CTLA-4 on purified CD8(+) T cells caused decreased proliferative responses to anti-CD3 stimulation and rapid loss of activation marker expression. In vivo, blockade of CTLA-4 by neutralizing anti-CTLA-4 mAb greatly

Gene Therapy for Mucopolysaccharidosis Type II-A Review of the Current Possibilities.

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder based on a mutation in the IDS gene that encodes iduronate 2-sulphatase. As a result, there is an accumulation of glycosaminoglycans-heparan sulphate and dermatan sulphate-in almost all body tissues, which leads to their dysfunction. Currently, the primary treatment is enzyme replacement therapy, which improves the course of the disease by reducing somatic symptoms, including hepatomegaly and splenomegaly. The enzyme, however, does not cross the blood-brain barrier, and no improvement in the function of the central nervous

Emerging therapies in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a rare, B cell non-Hodgkin's lymphoma with highly heterogeneous clinical presentation and aggressiveness. First-line treatment consists of intensive chemotherapy with autologous stem cell transplant for the fit, transplant eligible patients, or less intensive chemotherapy for the less fit (and transplant-ineligible) patients. Patients eventually relapse with a progressive clinical course. Numerous therapeutic approaches have emerged over the last few years which have significantly changed the treatment landscape of MCL. These therapies consist of targeted approach

Brentuximab vedotin prior to allogeneic stem cell transplantation increases survival in chemorefractory Hodgkin's lymphoma patients.

This study reports a retrospective multicenter experience by the Rete Ematologica Pugliese (REP) over the past 16 years, aiming to compare the patients characteristics and outcomes of 21 brentuximab vedotin (BV)-pre-treated patients to 51 patients who received reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT) without prior BV. In total, 72 patients with classical Hodgkin's lymphomas who received allogeneic SCT were retrospectively studied. Prior use of BV had no effect on either engraftment or the incidence and severity of acute graft versus host disease (GVHD). I

Risk of hospitalised infection in rheumatoid arthritis patients receiving biologics following a previous infection while on treatment with anti-TNF therapy.

BACKGROUND: The risk of subsequent infections in rheumatoid arthritis (RA) patients who receive biologic therapy after a serious infection is unclear. OBJECTIVE: To compare the subsequent risk of hospitalised infections associated with specific biologic agents among RA patients previously hospitalised for infection while receiving anti-tumour necrosis factor (anti-TNF) therapy. METHODS: Using 2006-2010 Medicare data for 100% of beneficiaries with RA enrolled in Medicare, we identified patients hospitalised with an infection while on anti-TNF agents. Follow-up began 61 days after hospital dis