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Therapeutic Vaccination (therapeutic + vaccination)
Selected AbstractsTHERAPEUTIC VACCINATION FOR CENTRAL NERVOUS SYSTEM REPAIRCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2006Beng Ti Ang SUMMARY 1Vaccination against infectious agents has been heralded as a triumph in modern medicine and, more recently, cancer vaccines have risen in prominence. The present review looks towards the use of vaccine therapy to attenuate damage after injury to the central nervous system (CNS). 2Significant debility is associated with brain injury, most commonly occurring as a result of physical trauma or stroke. This end result reflects the inability of neurons and axons to regenerate following injury to the CNS. This unconducive environment is due, in large part, to the presence of myelin and oligodendrocyte-related inhibitors of neurite outgrowth. 3We review how a vaccine-based approach has been variably used to circumvent this issue and promote axonal regeneration and repair following traumatic injury and other neurodegenerative disorders. In addition, emerging evidence suggests that the immune response to injury in the CNS may be manipulated so as to reduce cellular damage. Vaccine-directed approaches using this concept are also outlined. [source] Prospects for therapeutic vaccination with glatiramer acetate for neurodegenerative diseases such as Alzheimer's diseaseDRUG DEVELOPMENT RESEARCH, Issue 2 2002Michal Schwartz Abstract Neurodegenerative diseases, whatever their primary causes, are characterized by certain common features, one of which is their self-perpetuating nature. The ongoing progression of the disorder is due to the effects of destructive self-compounds, whose presence in the tissues is an outcome of the early phase of the disease and which gradually destroy remaining functional neurons. Studies in our laboratory have led to the recent formulation of a novel concept of protective autoimmunity as the body's mechanism of defense against these destructive self-compounds. This autoimmune response to central nervous system (CNS) insults is mediated by T-cells and presumably operates by activating and regulating local microglia and infiltrating macrophages (inflammatory response) to carry out their function of clearing destructive material from the tissue at risk. We suggest that a well-controlled autoimmunity counteracts and overcomes the destructive effects of the potentially harmful self-compounds, at the cost of some loss of tissue. An additional risk to the individual is the induction of an autoimmune disease, which is likely to occur if the autoimmune response is malfunctioning. An optimal balance of the various factors will lead to an outcome of maximal benefit at minimal cost to the tissue. A procedure for safely boosting the autoimmune response, by vaccination with a weak self-crossreactive antigen such as glatiramer acetate (also known as Cop-1) was found to protect rats from glutamate toxicity, a major mediator of the spread of damage and a well-known causative factor in neurodegenerative disorders. Cop-1, when administered according to a different regimen, is an FDA-approved drug for the treatment of multiple sclerosis. Different formulations of the same drug can therefore be used to treat two extreme manifestations of chronic degenerative diseases of the CNS. Drug Dev. Res. 56:143,149, 2002. © 2002 Wiley-Liss, Inc. [source] Preclinical development of hybrid cell vaccines for multiple myelomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2007Renata Walewska Abstract Immunotherapy may provide alternative or supplementary treatment of multiple myeloma (MM). We propose that hybrid cells, formed by fusing professional antigen-presenting cells with malignant plasma cells, would induce immune responses capable of mediating tumour regression. The human B-lymphoblastoid cell line, HMy2, was fused in vitro with CD138+ bead-separated myeloma plasma cells from five patients with MM. The hybrid cell lines generated in these studies grew stably in tissue culture, and maintained their phenotypic and functional characteristics, providing self-renewing cell lines with potential for therapeutic vaccination. The hybrid cells stimulated allogeneic and autologous T-cell proliferative responses in vitro to a considerably greater degree than their respective parent myeloma plasma cells, and directly activated both CD4+ and CD8+ T-cell responses. The enhanced T-cell stimulation correlated with expression of CD80 on the hybrid cells, and was inhibited by CTLA4-Ig fusion protein. The hybrid cell lines expressed several tumour-associated antigens known to be expressed in myeloma. These data show that self-replicating cell lines with enhanced immunostimulatory properties and potential for therapeutic vaccination can be generated by in vitro fusion of ex vivo myeloma cells and B-lymphoblastoid cell lines. [source] A pilot study of therapeutic vaccination with envelope protein E1 in 35 patients with chronic hepatitis CHEPATOLOGY, Issue 5 2003Frederik Nevens New treatments are needed for chronic hepatitis C patients in whom viral clearance cannot be achieved. Thirty-five chronic hepatitis C patients (genotype 1) were randomized to receive 20 ,g of recombinant HCV E1 (E1) (n = 26) or placebo (n = 9) intramuscularly at weeks 0, 4, 8, 12, and 24. Thirty-four then received open-label E1 vaccine at weeks 50, 53, 56, 59, 62, and 65. Twenty-four patients (12 men, 12 women; mean age, 52 y; 18 interferon-based treatment failures; mean baseline alanine aminotransferase [ALT] level, 118 IU/L) underwent a biopsy before and after 2 courses of E1, 17 months later. Liver histology was scored by 2 blinded pathologists according to the Ishak and Metavir systems. Postinjection reactions were similar to placebo (alum only). Nine of 24 patients (38%) had improvement of 2 points or more, 10 (41%) remained stable, and 5 (21%) showed worsening in total Ishak score. Nine patients (38%) improved both on Ishak and Metavir fibrosis scores. Plasma HCV-RNA levels remained unchanged, whereas ALT levels showed a trend toward a decrease during treatment. All but 3 patients developed a significant de novo E1-specific T-cell response. The increase in anti-E1 antibody levels correlated with the decrease in total Ishak score and with the relative decreases in both Ishak fibrosis score and ALT level (all P , .01). In conclusion, E1 therapeutic vaccination is well tolerated and the observed effects warrant further study. [source] Tumour immunology, vaccination and escape strategiesINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2003A. García-Lora Summary Our increasing knowledge of the mechanisms by which tumour cells escape immune effector cells is helping to establish new approaches to therapeutic vaccination against tumour development. One of the escape mechanisms used by tumour cells is the generation of multiple variants with different HLA phenotypes. These MHC class I phenotypic alterations play a key role in the tumour,host scenario, as they are crucial molecules for antigen presentation to T cells and modulation of natural killer (NK) cell activity. This review presents evidence indicating that tumours develop sophisticated MHC phenotypes that allow them to escape immune surveillance. We evaluate the importance of these alterations in terms of the potential development of therapeutic approaches to immune vaccination. [source] SHIV89.6P pathogenicity in cynomolgus monkeys and control of viral replication and disease onset by human immunodeficiency virus type 1 Tat vaccineJOURNAL OF MEDICAL PRIMATOLOGY, Issue 3-4 2000Aurelio Cafaro The Tat protein of human immunodeficiency virus (HIV) is produced very early after infection, plays a key role in the virus life cycle and in acquired immunodeficiency syndrome (AIDS) pathogenesis, is immunogenic and well conserved among all virus clades. Notably, a Tat-specific immune response correlates with non-progression to AIDS. Here, we show that a vaccine based on the Tat protein of HIV blocks primary infection with the simian/human immunodeficiency virus (SHIV)89.6P and prevents the CD4 T cell decline and disease onset in cynomolgus monkeys. No signs of virus replication were found in five out of seven vaccinated macaques for almost 1 year of follow-up. Since the inoculated virus (derived from rhesus or from cynomolgus macaques) is shown to be highly pathogenic in cynomolgus macaques, the results indicate efficacy of Tat vaccination in protection against highly pathogenic virus challenge. Finally, the studies of the Tat-specific immunological responses indicate a correlation of protection with a cytotoxic T cell response. Thus, a Tat-based vaccine is a promising candidate for preventive and therapeutic vaccination in humans. [source] Particulate delivery systems for vaccines: what can we expect?JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2006Vincent W. Bramwell In our attempts to thwart the unwanted attentions of microbes by prophylactic and therapeutic vaccination, the knowledge of interactions at the molecular level may prove to be an invaluable asset. This article examines how particulate delivery systems such as liposomes and polymer micro-spheres can be applied in the light of recent advances in immunological understanding. Some of the biological interactions of these delivery systems are discussed with relevance for antigen trafficking and molecular pathways of immunogenicity and emphasis on the possible interaction of liposomal components. In particular, traditional concepts such as antigen protection, delivery to antigen presenting cells and depot formation remain important aspects, whilst the inclusion of selected co-adjuvants and enhanced delivery of these moieties in conjunction with antigen now has a firm rationale. [source] Monocyte-derived dendritic cells from HCV-infected patients transduced with an adenovirus expressing NS3 are functional when stimulated with the TLR3 ligand poly(I:C)JOURNAL OF VIRAL HEPATITIS, Issue 11 2008I. Echeverría Summary., Dendritic cells (DC) transfected with an adenovirus encoding hepatitis C virus (HCV) NS3 protein (AdNS3) induce potent antiviral immune responses when used to immunize mice. However, in HCV infected patients, controversial results have been reported regarding the functional properties of monocyte-derived DC (MoDC), a cell population commonly used in DC vaccination protocols. Thus, with the aim of future vaccination studies we decided to characterize MoDC from HCV patients transfected with AdNS3 and stimulated with the TLR3 ligand poly(I:C). Phenotypic and functional properties of these cells were compared with those from MoDC obtained from uninfected individuals. PCR analysis showed that HCV RNA was negative in MoDC from patients after the culture period. Also, phenotypic analysis of these cells showed lower expression of CD80, CD86, and CD40, but similar expression of HLA-DR molecules as compared to MoDC from uninfected individuals. Functional assays of MoDC obtained from patients and controls showed a similar ability to activate allogeneic lymphocytes or to produce IL-12 and IL-10, although lower IFN-, levels were produced by cells from HCV patients after poly(I:C) stimulation. Moreover, both groups of MoDC induced similar profiles of IFN-, and IL-5 after stimulation of allogeneic T-cells. Finally, migration assays did not reveal any difference in their ability to respond to CCL21 chemokine. In conclusion, MoDC from HCV patients are functional after transduction with AdNS3 and stimulation with poly(I:C). These findings suggest that these cells may be useful for therapeutic vaccination in chronic HCV infection. [source] The effects of CpG-C oligodeoxynucleotides on innate immune responses in Eriocheir sinensis (H. Milne-Edwards, 1853)AQUACULTURE RESEARCH, Issue 10 2010Ying Zhang Abstract CpG oligodeoxynucleotides (ODNs) can stimulate the immune system, and therefore are widely used as a therapeutic vaccination and immune adjuvant in human. In the present study, CpG-C, a combination of A- and B-class ODN, was injected into Chinese mitten crab Eriocheir sinensis at three doses (0.1, 1 and 10 ,g crab,1), and the reactive oxygen species (ROS) levels, activities of total intracellular phenoloxidase (PO) and lysozyme-like activities, the mRNA transcripts of EsproPO, EsCrustin and EsALF were assayed to evaluate its modulating effects on the immune system of crab. The ROS levels in all treated and control groups were significantly increased from 6 to 24 h, except that ROS in 0.1 ,g CpG-C-treated crabs was comparable to that of the blank at 6 h. The PO activity was significantly enhanced and EsproPO transcripts were down-regulated (P<0.01) at 6 h after the injection of 0.1 ,g CpG-C, with no significant changes in the other dosage treatments. The lysozyme-like activities and EsCrustin transcripts in the CpG-C-treatment groups were significantly higher than those of controls. The mRNA expression of EsALF remained almost constant in all the groups during the treatment. These results collectively suggested that CpG-C could activate the immune responses of E. sinensis, and might be used as a novel immunostimulant for disease control in crabs. [source] | ||||||||||