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1

Interleukin-2 receptor targeted immunotherapy-an attempt at synthesis

100%
Sablinski T., Wasik M. A., Tilney N. L., Kupiec-Weglinski J. W.
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vol. 46
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issue 3
275-285
EN
Recent findings on the structure of IL-2R and the therapeutic applications of anti IL-2R directed modalities such as monoclonal antibodies, IL-2 toxin hybrids are discussed in this paper.
2

Allergen-specific T lymphocytes as targets for specific immunotherapy: striking at the roots of type I allergy

80%
Bohle B.
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issue 4
233-242
EN
In the past decades allergic diseases have tremendously increased and hypersensitivity reactions now represent a growing health concern in industrialized countries. Despite various effective therapeutic options for the treatment of allergic diseases, only specific immunotherapy (SIT) has been shown to have effects on the underlying immunological mechanisms, namely functional changes at the level of T helper lymphocytes (Th). It was found that allergen-specific CD4+ Th2 lymphocytes play a key role in the pathophysiology of atopic diseases. During successful SIT, the Th2-dominated immune response is modified towards a Th1 response, leading to a decline in allergen-specific IgE levels in the long term. In order to improve the efficacy and safety of SIT, novel approaches were developed targeting allergen-specific Th2 lymphocytes since specific inactivation or modulation towards Th1 cells could interfere with the disease process. In view of this aspect, this review will basically focus on two new promising approaches to improve SIT: 1) the use of hypoallergenic proteins characterized by reduced IgE-binding capacities but retained T lymphocyte-activating properties and 2) oligodeoxynucleotides containing CpG motifs as an example of adjuvants which foster Th1 immune responses. Both approaches promise to be capable of adjusting the pathological Th2 immune response.
3

Cancer immunogene therapy

80%
Yoshizawa H., Kagamu H., Gejyo F.
Archivum Immunologiae et Therapiae Experimentalis
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2001
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vol. 49
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issue 5
337-344
EN
The establishment of cancer in a host involves at least two major events: the escape of tumor cells from normal growth control and their escape from immunological recognition. Because of this nature of their development, cancer cells seem to be predominatly poorly immunogenic. In contrast to the previous idea that cancer cells express no recognizable antigens, recent progress in the identification and characterization of tumor antigens, as well as the expansion of knowledge on the cellular and molecular mechanisms of antigen recognition by the immune system, have raised the possibility of using immunotherapy to treat certain tumors. Information on these mechanisms has been obtained in three crucial areas: 1) the role of cytokines in the regulation of the immune response, 2) the molecular characterization of tumor antigens in both mouse and human tumors, and 3) the molecular mechanisms of T cell activation and antigen presentation. Such information has provided new insight into tumor immunology and immunotherapy. Furthermore, recombinant DNA technology allows for modification of the genome of mammalian cells for therapeutic purposes in several diseases. Several novel strategies have been developed to derive genetically modified tumor cells and use them as cellular vaccines to induce antitumor immunity in animal tumor models. This combined modality of genetically modified tumor cells and immunotherapy has been termed immunogene therapy of tumors. Crucial to this approach has been the ability to transfer into normal or neoplastic cells genes known to increase the immunogenicity of cells, which subsequently can be used to augment immune reactions in tumor-bearing mice or cancer patients. While there has been success in inducing antitumor immunity in some tumor models, there are difficulties and limitations in the application of these gene-modified tumor cells for the treatment of preexisting tumors. In this review, recent progress in cancer immunogene therapy is discussed.
4

Experimental therapies for psoriasis

80%
Asadullah K., Volk H.-D., Friedrich M., Sterry W.
Archivum Immunologiae et Therapiae Experimentalis
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2002
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vol. 50
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issue 6
409-418
EN
There is a high medical need for better therapies for psoriasis. Based on new insight into the pathophysiology of this frequent immune disease, a number of novel systemic immunomodulatory therapies are currently in clinical development. These include approaches targeting antigen presentation and costimulation, T cell activation and leukocyte adhesion, action of proinflammatory mediators, and modulating the cytokine balance. Although mainly only preliminary data are available so far, these trials contribute to a further understanding of the disease and will eventually lead to new therapeutic options for psoriasis. Moreover, since psoriasis can be considered as a visible model disease for T cell-mediated disorders characterized by a type 1 cytokine pattern in general, such approaches may have impact for other immune disorders as well. Here we review the rationale and the initial clinical data of these important recent experimental therapies.
5

Tumor resistance to CD8+ T cell-based therapeutic vaccination

80%
Huang Y., Shah S., Qiao L.
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2007
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vol. 55
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issue 4
205-217
EN
CD8+ cytotoxic T lymphocytes (CTLs) play an important role in antitumor immunity. Induction of tumor-specific CTLs is one major strategy for tumor immunotherapy. However, therapeutic vaccinations used to treat firmly established tumors are generally ineffective. A thorough understanding of the mechanisms underlying tumor resistance to CTL-based therapeutic vaccination is very important in the tumor immunology field. There are two main mechanisms by which tumors develop resistance to CTL-based therapeutic vaccinations. One is that tumors induce peripheral tolerance of tumor-specific CD8+ T cells. The other is that tumor cells themselves develop immune evasion mechanisms to prevent recognition and killing by CTLs. This review focuses on recently reported cellular and molecular mechanisms of CD8+ T cell tolerance and immune evasion in tumors and discusses about the possibilities to improve tumor immunotherapy.
6

Specific immunotherapy stimulates the binding of histamine H2 receptor antagonist by lymphocytes

80%
Zak-Nejmark T., Malolepszy J., Nadobna G., Kuczynska-Sekieta K., Marczynska-Sarul E., Jutel M.
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vol. 40
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issue 2
113-116
EN
The binding of antagonists of histamine receptors H1 (ranitidine) by perpheral blood lymphocytes from pollinotics was determined before and after the course of immunotherapy. We found that lymphocytes from atopic subjects showed significant decrease in the binding of H2 receptor antagonist as compared to control subjects. specific immunotherapy induced statistically significant increase in H2 receptor antagonist binding, which correlated with the improvement of clinical symptoms.
7

Tumor vaccines for the management of prostate cancer

80%
McNeel D. G., Disis M. L.
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vol. 48
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issue 2
85-93
EN
Prostate cancer is a significant health problem and one of the leading causes of cancer-related death among men. Given the typically long natural history of the disease, there is considerable interest in developing new therapies to treat or prevent metastatic disease, and cancer vaccines are a particularly attractive immune-based approach. Early clinical studies using non-specific immunomodulatory treatments have met with limited success, but also suggest that improved immunologic approaches might be useful in treating human prostate cancer. Over the last decade, the identification of immune cells responsible for actual destruction of prostate tissue and advances in immunologic and molecular techniques have led to a variety of vaccination approaches that are currently being evaluated in human clinical trials. The present article discusses the rationale in animal models for particular immunization strategies and describes the vaccines currently being used in patients with prostate cancer. The ongoing identification of tumor antigens and proteins involved in prostate cancer progression and the development of better immunologic animal models suggest a hopeful future for the design of effective prostate cancer vaccines.
8

Considerations on clinical use of T Cell immunotherapy for cancer

80%
Plautz G. E., Cohen P. A., Shu S.
Archivum Immunologiae et Therapiae Experimentalis
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2003
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vol. 51
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issue 4
245-257
EN
The recognition by effector T lymphocytes of novel antigenic targets on tumor cells is the premise of specific targeted immunotherapy of cancer. With the molecular characterization of peptide epitopes from melanoma antigens, and more recently broadly expressed tumor antigens, there has been considerable enthusiasm for clinical evaluation of peptide tumor vaccines. Immunologic monitoring of vaccinated patients has demonstrated expansion of CD8+ T cells that react with the relevant peptide and, more importantly, with native tumor. In most instances however, vaccine-induced CD8+ T cell responses alone have not been sufficiently robust or sustained to translate into a high percentage of durable clinical responses. Vaccine strategies have also utilized dendritic cells (DCs) that have been modified to present tumor antigens. The superior antigen processing capacity and co-stimulatory function of DC convey a powerful stimulatory signal to both CD4+ and CD8+ T cells. Several strategies are attempting to broaden the immune response beyond single antigens by introducing the entire complement of tumor antigens into DCs. Adoptive immunotherapy is a promising strategy to recover tumor-reactive precursor T cells from patients, stimulate them to induce numerical expansion, and then re-infuse them. Ex vivo manipulation of the tumor-reactive T cells also permits cytotoxic therapy to be administered to the patient without damaging the effector cells. Recently, host lymphodepletion prior to adoptive transfer of effector T cells has resulted in an extremely high and sustained frequency of effectors that has achieved therapeutic efficacy against bulky metastatic disease in a substantial fraction of treated patients.
9

Enhancing cytotoxic t cell responses with altered-peptide ligands

80%
Zhao R., Collins E. J.
Archivum Immunologiae et Therapiae Experimentalis
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2001
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vol. 49
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issue 4
271-278
EN
Interest in class I MHC-mediated immunotherapy is growing rapidly. In order to fight a virus or cancer effectively, a successful immunotherapeutic must activate a large number of specific CD8+ T cells and also generate immunological memory. Attempts to generate immune responses towards tumor- or virus-derived peptides have frequently been frustrated by the nature of the peptide antigen itself. Either the peptide does not bind well to its cognate MHC, or the T cells directed towards it have been functionally inactivated in vivo. Altered-peptide ligands are an effective way to circumvent these problems. However, generating enhanced binding of altered peptides to class I MHC while still maintaining recognition of the wild-type peptide is not straightforward. Many groups design enhanced binding peptides by substituting the observed anchor residues with those that are most preferred by the class I MHC molecule. For many antigenic peptides, this approach does not work. Furthermore, if a higher affinity peptide is designed, the substitutions may result in reduced recognition by CD8+ T cells. Therefore, the design of an altered-peptide ligand requires careful testing of each candidate therapeutic in terms of affinity for class I MHC and immunological reactivity. Lastly, immunotherapy using class I MHC must also take into account the large genetic heterogeneity in the population. A therapeutic that is only effective for 5-10 percent of the population is not as attractive as one that works for over 90% of the population. The use of MHC supertypes (groups of class I MHC allotypes that share similar peptide-binding characteristics) shows great promise in overcoming this problem.
10

Effective tumor immunotherapy: start the engine, release the brakes, step on the gas, ...and get ready to face autoimmunity

80%
Tirapu I., Mazzolini G., Rodriguez-Calvillo M., Arina A., Palencia B., Gabari I., Melero I.
Archivum Immunologiae et Therapiae Experimentalis
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2002
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vol. 50
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issue 1
13-18
EN
Cellular immune responses can destroy cancer cells, achieving the cure of experimental malignancies. An expanding wealth of knowledge on the molecular basis of how to prime and amplify a T cell response has fueled a number of strategies successful at treating established tumors (rather than merely preventing tumor grafting). The most efficacious approaches operate at different stages, including: 1) priming the immune response using tumor antigen-expressing dendritic cells or tumor cells transfected with genes that render them immunogenic, 2) sustaining and amplifying immunity using agonistic monoclonal antibodies against costimulatory molecules or immune-potentiating cytokines, and 3) eliminating mechanisms that self-regulate the strength of the immune response, such as inhibitory receptors or regulatory T cells. A rational combination of such approaches holds great hope for cumulative and synergistic effects, but there is also evidence that they can open the flood-gates for unwanted inflammatory reactions. The next decade can be envisioned as the time when the first reproducibly efficacious combination regimes for cancer immunotherapy will become available and widely used in the clinic, as clinicians learn the best strategies and try to harness their potentially damaging effects.
11

Cytokine-based immunotherapy of allergic disease

80%
Lewkowich I. P., HayGlass K. T.
Archivum Immunologiae et Therapiae Experimentalis
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2001
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vol. 49
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issue 4
293-302
EN
Human immediate hypersensitivity diseases are strongly associated with an excessive type 2 response to normally innocuous environmental antigens, and are a growing health care concern in developed nations. Commonly prescribed treatments provide effective symptomatic relief, but are unable to consistently ameliorate the underlying cause of allergic disease: the excessive generation of allergen specific Th2 cells. IL-12 and IL-18 are potent inducers of type 1 immunity, and, as such, have been proposed as candidates for treatment of allergic diseases. This review critically assesses the potential of recombinant IL-12 and IL-18 immunotherapy to redirect both de novo and established allergic responses in animal models of human allergic disease to clinically protective immune responses.
12

Immunotherapy of rheumatoid arthritis targeting inflammatory cytokines and autoreactive T cells

80%
Chen G.
Archivum Immunologiae et Therapiae Experimentalis
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2010
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vol. 58
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issue 1
27-36
EN
Rheumatoid arthritis is a chronic disorder for which there is no known cure. Concentrating on specific elements of the abnormal immune response that characterizes the disease, scientists are reaching into biotechnology's bag of tricks to develop immunotherapeutic techniques. This paper will present some advances in the immunotherapy of rheumatoid arthritis targeting inflammatory cytokines and autoreactive T cells.
13

Immunotherapy in the management of sepsis

70%
Sikora J. P.
Archivum Immunologiae et Therapiae Experimentalis
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2002
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vol. 50
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issue 5
317-324
EN
The work presents the role of Gram-negative bacteria endotoxins, pro- and anti-inflammatory cytokines and reactive oxygen species (ROS) in the complex and not fully explained pathogenesis of sepsis. The so called ?respiratory burst? of neutrophils and antioxidant mechanisms of the host are also discussed. The work has focused on possible approaches to the management of sepsis connected with immunotherapy. Neutralisation of endotoxin lypopolysaccharide (LPS), anti-TNF-alpha therapy with monoclonal antibodies or pentoxifylline (PTXF) as well as soluble recombinant cytokine agonists and antagonists used in clinical trials were taken into consideration. Besides, cytokine manipulation therapy, anti-adhesion techniques or glicocorticoides and antioxidant barrier interference were also described. So far there has been no immunotherapy of sepsis in children of proven clinical efficacy, which prompts aggressive examination of the immune system, aimed at affecting its function.
14

Immunotherapy of inflammatory bowel diseases: current concepts and future perspectives

70%
Neurath M. F.
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vol. 48
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issue 2
81-84
EN
The etiology and the pathogenesis of inflammatory bowel diseases (IBD), e. g. Crohn's disease and ulcerative colitis are still not completely understood. However, there is growing evidence that an alteration of the mucosal immune system towards luminal antigens in a genetically susceptible host plays a key role in the pathogenesis of IBD. In particular, cytokines produced by intestinal epithelial cells, lamina propria macrophages and CD4+ T cells appear to contribute to the initiation and perpetuation of intestinal inflammation in IBD. This review focuses on the role of the mucosal immune system in the pathogenesis of IBD and potential novel immunotherapeutic strategies for chronic intestinal inflammation. Such strategies include recombinant antiinflammatory cytokines, neutralizing antibodies or fusion proteins, antisense oligonucleotides and adenoviral gene transfer.
15

Dendritic cells and their application in cancer immunotherapy - achievements and future prospects

70%
Rossowska J., Pajtasz-Piasecka E.
Postępy Higieny i Medycyny Doświadczalnej
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2003
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vol. 57
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issue 5
501-518
EN
Dendritic cells (DC) are generally believed to play a key role in the initiation of immune response. A potential usefulness of these cells in antitumor immunotherapy is strongly considered in every stage of cancer treatment. Studies on tumor tissue infiltration by immune cells shown, that DC represented only a small percentage of leukocytes. The influence of tumor environment resulted in reduction of DC number, their inability to migrate across endothelial barriers, or impaired maturation and efficiency of tumor antigens presentation. Thus, decreased number of DC in tumors could be associated with a bad prognosis. Many attempts concentrate on the creation of the DC-based vaccines, which would generate strong anticancer cell mediated immunity. They include studies on stage of differentiation of the administered DC; effective way for antigen loading; optimum route and schedule of DC delivery into tumor bearing host; effective vectors for the therapeutic genes; effects of the therapy based on cytokine secreting DC; influence of DC on co-operation between innate and acquired immunity as well as on the generation of specific antitumor response. This review is focused on two important areas aiming for the preparation of DC vaccine for effective stimulation of immune response: - loading of DC with tumor antigens (or other ways of DC preparation to successful antigen presentation) - as an encouraging evidence of therapeutic efficacy, and - genetic modification of DC with cytokines resulting in the stimulation or alteration of the antitumor DC activity - as a promising anticancer strategy.
16

Modulation of pulmonary innate immunity during bacterial infection: animal studies

70%
Schultz M. J., van_ d. P. T.
Archivum Immunologiae et Therapiae Experimentalis
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2002
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vol. 50
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issue 3
159-168
EN
Both the increasing number of immunocompromised patients susceptible to pneumonia, and the development of bacterial resistance are significant problems related to the treatment of pneumonia. The primary outcome of treatment for pneumonia is to tip the balance to a successful host response. An ideal approach would be the combination of immunomodulation and conventional antimicrobial therapy for the treatment of pneumonia. It is of increasing importance to understand the components of innate immunity, before immunomodulatory therapy can be applied to patients. Much of our knowledge of the role of alveolar macrophages, cytokines and chemokines in the pathogenesis of pneumonia is derived from animal studies on experimental pneumonia. This article summarizes current information on the role of an alveolar macrophage (AM) and AM-derived mediators in host defense against pneumonia.
17

Interleukin-2 gene therapy potentiates tha antitumor effect of cytostatic agent in mice with advanced transplantable tumors

70%
Pajtasz-Piasecka E., Radzikowski C.
Biotechnologia
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1996
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issue 4
68-79
EN
The combination of one dose of the cytostatic agent (bromoanalog of ifosfamide) administration with subsequent peritumoral injections of the cytokine-producing cells was observed to be more efficient in the tumor growth inhibition as compared with the cytostatic alone.
18

Nanovesicular vaccines: exosomes

70%
Li X., Zhang Z., Beiter T., Schluesener H. J.
Archivum Immunologiae et Therapiae Experimentalis
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2005
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vol. 53
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issue 4
329-335
EN
Exosomes are small membrane vesicles derived from late endosome. They are about 30?100 nm in diameter. The secretion of exosomes is a process in which multivesicular bodies fuse with the cell membrane, and all cells that contain multivesicular endocytic compartments could theoretically secrete exosomes. The surprising biological functions of exosomes are only slowly being unveiled, but it is already clear that they serve to remove obsolete membrane proteins and act as messages of inter-cellular communication. Exosomes derived from tumor or antigen-presenting cells have been extensively investigated. They are released into the extracellular environment and fuse with the membranes of neighboring cells, delivering membrane and cytoplasmic proteins from one cell to another. Exosomes carry immunorelevant structures which play important roles in immune response, such as MHC molecules, costimulatory molecules, heat shock proteins, and naive tumor antigens. Therefore they have been suggested as potential vaccines. Consequently, exosomes have shown considerable anti-tumor effect in several studies and are in phase I clinical trials.
19

Regulatory T cells: magic bullets for immunotherapy?

61%
Frey O., Brauer R.
Archivum Immunologiae et Therapiae Experimentalis
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2006
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vol. 54
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issue 1
33-43
EN
In the past few years it has been become increasingly clear that T cells capable of actively suppressing immune responses are thought to be in part responsible for the maintenance of peripheral self tolerance. In healthy rodents and humans, CD4+ T cells constitutively expressing the interleukin (IL)-2 receptor -chain (CD25) are able to exert such suppressive function in vitro and in vivo. Despite great efforts in our understanding of the biology of such immunoregulatory T cells, there are still certain points incompletely understood. Although some authors suggest that immunoregulatory cytokines such as IL-10 or transforming growth factor b are critical for the suppressive effect of these cells, this is controversial and the exact molecular nature and the targets of suppression are largely unknown. Thus far, until regulatory T cells can be used for diagnostic or therapeutic purposes many questions have to be answered. In this review we summarize the current knowledge on the function and properties of this T cell subset and discuss their potential role in human autoimmune or chronic inflammatory diseases.
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