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‣ Specific immunotherapy using Hymenoptera venom: systematic review; Imunoterapia específica com venenos de Hymenoptera: revisão sistemática

WATANABE, Alexandra Sayuri; FONSECA, Luiz Augusto Marcondes; GALVÃO, Clóvis Eduardo Santos; KALIL, Jorge; CASTRO, Fabio Fernandes Morato
Fonte: Associação Paulista de Medicina - APM Publicador: Associação Paulista de Medicina - APM
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
36.920166%
CONTEXT AND OBJECTIVE: The only effective treatment for patients who have severe reactions after Hymenoptera stings is venom immunotherapy. The aim of this study was to review the literature to assess the effects of venom immunotherapy among patients presenting severe reactions after Hymenoptera stings. DESIGN AND SETTING: Randomized controlled trials in the worldwide literature were reviewed. The manuscript was produced in the Discipline of Allergy and Clinical Immunology, Universidade de São Paulo (USP). METHODS: Randomized controlled trials involving venom immunotherapy versus placebo or only patient follow-up were evaluated. The risk of systemic reactions after specific immunotherapy was evaluated by calculating odds ratios (OR) and their 95% confidence intervals. RESULTS: 2,273 abstracts were identified by the keywords search. Only four studies were included in this review. The chi-square test for heterogeneity showed that two studies were homogeneous and could be included in a meta-analysis. By combining the two studies, the odds ratio became significant: 0.29 (0.10-0.87). However, analysis on the severity of the reactions after immunotherapy showed that the benefits may not be so significant because the reactions were mostly similar to or milder than the original reaction. CONCLUSIONS: Specific immunotherapy should be recommended for adults and children with moderate to severe reactions...

‣ Phase I trial of DNA-hsp65 immunotherapy for advanced squamous cell carcinoma of the head and neck

MICHALUART, P.; ABDALLAH, K. A.; LIMA, F. D.; SMITH, R.; MOYSES, R. A.; COELHO, V.; VICTORA, G. D.; SOCORRO-SILVA, A.; VOLSI, E. C.; ZARATE-BLADES, C. R.; FERRAZ, A. R.; BARRETO, A. K.; CHAMMAS, M. C.; GOMES, R.; GEBRIM, E.; ARAKAWA-SUGUENO, L.; FERNANDES
Fonte: NATURE PUBLISHING GROUP Publicador: NATURE PUBLISHING GROUP
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
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Considering that mycobacterial heat-shock protein 65 (hsp65) gene transfer can elicit a profound antitumoral effect, this study aimed to establish the safety, maximum-tolerated dose (MTD) and preliminary efficacy of DNA-hsp65 immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). For this purpose, 21 patients with unresectable and recurrent HNSCC were studied. Each patient received three ultrasound-guided injections at 21-day intervals of: 150, 600 or 400 mu g of DNA-hsp65. Toxicity was graded according to CTCAE directions. Tumor volume was measured before and after treatment using computed tomography scan. The evaluation included tumor mass variation, delayed-type hypersensitivity response and spontaneous peripheral blood mononuclear cell proliferation before and after treatment. The MTD was 400 mg per dose. DNA-hsp65 immunotherapy was well tolerated with moderate pain, edema and infections as the most frequent adverse effects. None of the patients showed clinical or laboratory alterations compatible with autoimmune reactions. Partial response was observed in 4 out of 14 patients who completed treatment, 2 of which are still alive more than 3 years after the completion of the trial. Therefore, DNA-hsp65 immunotherapy is a feasible and safe approach at the dose of 400 mg per injection in patients with HNSCC refractory to standard treatment. Further studies in a larger number of patients are needed to confirm the efficacy of this novel strategy.; CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico); FINEP ( Financiadora de Estudos e Projetos)

‣ Revisão sistemática: imunoterapia específica para venenos de hymenoptera; Systematic review: specific immunotherapy for Hymenoptera venoms

Watanabe, Alexandra Sayuri
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 14/09/2006 Português
Relevância na Pesquisa
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A hipersensibilidade a veneno de Hymenoptera representa importante problema do ponto de vista de saúde da população, uma vez que pacientes alérgicos aos componentes do veneno podem desenvolver reações graves, às vezes fatais. A única profilaxia efetiva em pacientes sensibilizados é a imunoterapia veneno específica. Objetivos: avaliar as evidências científicas a respeito dos efeitos da imunoterapia específica utilizada na profilaxia secundária das reações graves em pacientes sensibilizados a veneno de Hymenoptera, por meio da realização de uma revisão sistemática. Métodos: a estratégia de busca seguiu as recomendações do Grupo de Pele da Colaboração Cochrane. A pesquisa foi realizada nas seguintes bases de dados: MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), EMBASE, LILACS, SciSEARCH e nas referências de artigos mais relevantes. Todos os ensaios clínicos controlados e randomizados envolvendo imunoterapia com veneno de Hymenoptera versus imunoterapia com placebo ou apenas seguimento dos pacientes foram avaliados. Dois revisores de forma independente (ASW e LAMF) avaliaram a elegibilidade e a qualidade metodológica de cada ensaio clínico e extraíram os dados. O risco de reações sistêmicas...

‣ Efeito da imunoterapia com Dermatophagoides pteronyssinus na resposta clínica e imunológica ao camarão; Effect of immunotherapy with Dermatophagoides pteronyssinus in the clinical and immunological response to shrimp

Yang, Ariana Campos
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 30/07/2009 Português
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Objetivo: O objetivo desse estudo foi avaliar alterações na resposta clínica e imunológica ao camarão após a imunoterapia com Dermatophagoides pteronyssinus. Métodos: Selecionou-se 35 indivíduos alérgicos a Dermatophagoides pteronyssinus (Der p), os quais foram submetidos a testes cutâneos de leitura imediata para ácaros, baratas, camarão, tropomiosina recombinante, além de cão, gato e fungos. A detecção de IgE espcífica in vitro foi feita para o ácaro, camarão, barata americana e para suas tropomiosinas. Em todos, avaliou-se reatividade clínica ao camarão através de provocação oral. Dez pacientes foram alocados para o grupo controle, e 25 foram submetidos à imunoterapia alérgeno específica para o ácaro. Os testes cutâneos e a dosagem de IgE sérica específica foram repetidas após a indução da imunoterapia, e após 1 ano do início. A reatividade clínica ao camarão foi reavaliada no final do estudo pela provocação oral. Resultados: No grupo dos pacientes que foram submetidos à imunoterapia, observamos diminuição na reatividade nos testes cutâneos e dosagem de IgE específica para Der p, camarão e tropomiosina recombinante. Dos 10 pacientes com testes cutâneos positivos para camarão, 4 foram negativos na dosagem após um ano de imunoterapia (p= 0...

‣ Imunoterapia específica : efeitos sobre granulócitos de pacientes alérgicos ao veneno de Apis Mellifera; Specific immunotherapy : Effects on granulocytes from Apis Mellifera allergic patients

Karla Priscila Vieira Ferro
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 24/11/2011 Português
Relevância na Pesquisa
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As reações alérgicas à ferroada de inseto resultam de resposta exacerbada do sistema imune, com produção de elevados níveis de anticorpos IgE alérgeno-específicos e padrão de citocinas Th2, envolvidas na diferenciação de linfócitos B específicos para aquele antígeno em células produtoras de IgE e recrutamento de células efetoras da resposta alérgica. Neste contexto, granulocitos são células efetoras importantes na fase tardia da resposta alérgica e estão envolvidos na patogênese de diferentes doenças. Eosinófilos e neutrófilos, especificamente, modulam a resposta imune por meio de diferentes mecanismos, como a secreçao de citocinas, quimiocinas e mediadores lipídicos. A IgE desempenha papel central na patogênese das doenças alérgicas, interagindo com dois receptores de membranas: alta afinidade FcsRI e baixa afinidade FcsRII (CD23). A ligação da IgE ao seu receptor em mastocitos e basófilos promove a liberação de mediadores inflamatórios, dentre eles, a histamina. A histamina além de induzir os sintomas agudos da reação alérgica, sustenta a reação inflamatória até a fase crônica, sendo estes efeitos mediados através da ativação de diferentes receptores (H1, H2, H3 e H4). Os fatores liberadores de histamina (HRF)...

‣ Veiculação de mRNA de células tumorais em lipossomas catiônicos para imunoterapia do câncer; Cationic liposomes as carriers of mRNA from tumor cells for cancer immunotherapy

Micaela Tamata Vitor
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 16/04/2013 Português
Relevância na Pesquisa
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Esta pesquisa teve como objetivo o desenvolvimento tecnológico de uma vacina lipossomal contendo RNA tumoral destinado à imunoterapia do câncer. Nesta estratégia, RNA total codificando o antígeno tumoral Her-2/neu extraído de linhagem de células de adenocarcinoma de mama humano SK-BR-3 foram incorporados em lipossomas catiônicos introduzidos in vitro em células dendríticas (DCs). A vacina de DCs tem a função de auxiliar o sistema imunológico a identificar antígenos tumorais para que as células cancerígenas sejam eliminadas. Porém uma das etapas críticas é a introdução (transfecção) de RNA nas DCs. Lipossomas catiônicos é uma alternativa promissora, pois além de ativarem as DCs, é capaz mediar a transfecção de ácidos nucléicos para células. A experiência prévia do grupo de pesquisa na área de lipossomas catiônicos mostrou a possibilidade da obtenção de lipossomas em larga escala para o desenvolvimento de vacina de DNA contra a tuberculose. Neste contexto, este trabalho avaliou os lipossomas catiônicos com a composição lipídica de fosfatidilcolina natural de ovo (EPC), 1,2-dioleoil-sn-glicero-3-fosfatidiletanolamina (DOTAP) e 1,2-dioleoil-3-trimetilamônio-propano (DOPE), na respectiva proporção molar de 50/25/25%. Metodologicamente...

‣ Specific immunotherapy using Hymenoptera venom: systematic review

Watanabe,Alexandra Sayuri; Fonseca,Luiz Augusto Marcondes; Galvão,Clóvis Eduardo Santos; Kalil,Jorge; Castro,Fabio Fernandes Morato
Fonte: Associação Paulista de Medicina - APM Publicador: Associação Paulista de Medicina - APM
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2010 Português
Relevância na Pesquisa
36.920166%
CONTEXT AND OBJECTIVE: The only effective treatment for patients who have severe reactions after Hymenoptera stings is venom immunotherapy. The aim of this study was to review the literature to assess the effects of venom immunotherapy among patients presenting severe reactions after Hymenoptera stings. DESIGN AND SETTING: Randomized controlled trials in the worldwide literature were reviewed. The manuscript was produced in the Discipline of Allergy and Clinical Immunology, Universidade de São Paulo (USP). METHODS: Randomized controlled trials involving venom immunotherapy versus placebo or only patient follow-up were evaluated. The risk of systemic reactions after specific immunotherapy was evaluated by calculating odds ratios (OR) and their 95% confidence intervals. RESULTS: 2,273 abstracts were identified by the keywords search. Only four studies were included in this review. The chi-square test for heterogeneity showed that two studies were homogeneous and could be included in a meta-analysis. By combining the two studies, the odds ratio became significant: 0.29 (0.10-0.87). However, analysis on the severity of the reactions after immunotherapy showed that the benefits may not be so significant because the reactions were mostly similar to or milder than the original reaction. CONCLUSIONS: Specific immunotherapy should be recommended for adults and children with moderate to severe reactions...

‣ Post-exposure treatment of Ebola virus using passive immunotherapy: proposal for a new strategy

Chippaux,Jean-Philippe; Boyer,Leslie V; Alagón,Alejandro
Fonte: Centro de Estudos de Venenos e Animais Peçonhentos - CEVAP, Universidade Estadual Paulista - UNESP Publicador: Centro de Estudos de Venenos e Animais Peçonhentos - CEVAP, Universidade Estadual Paulista - UNESP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2015 Português
Relevância na Pesquisa
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Background Better treatments are urgently needed for the management of Ebola virus epidemics in Equatorial Africa. Methods We conducted a systematic review of the literature on the use of passive immunotherapy for the treatment or prevention of Ebola virus disease. We placed findings from this review into the context of passive immunotherapy currently used for venom-induced disease, and recent improvements in manufacturing of polyvalent antivenom products. Results Passive immunotherapy appears to be one of the most promising specific treatments for Ebola. However, its potential has been incompletely evaluated, considering the overall experience and recent improvement of immunotherapy. Development and use of heterologous serum derivatives could protect people exposed to Ebola viruses with reasonable cost and logistics. Conclusion Hyperimmune equine IgG fragments and purified polyclonal whole IgG deserve further consideration as treatment for exposure to the Ebola virus.

‣ Allergen-Specific Immunotherapy in Patients 55 Years and Older: Results and Review of Literature

Baptistella,Eduardo; Maniglia,Sergio; Malucelli,Diego Augusto; Rispoli,Daniel; Silva,Thanara Pruner de; Tsuru,Fernanda Miyoko; Becker,Renata Vecentin; Bernardi,Gustavo; Dranka,Daniela; Ferraz,Bruno
Fonte: Fundação Otorrinolaringologia Publicador: Fundação Otorrinolaringologia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2013 Português
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Introduction  Over the years the immune system suffers many morphologic and functional alterations, which result in a peak of function in puberty and a gradual decrease in the elderly. Aim  Treat patients 55 years or older with allergic rhinitis with immunotherapy and then analyze the response to allergens. Materials and Methods  From June 2009 to July 2010, 104 charts of patients 55 years or older with allergic complaints were evaluated. The patients were selected by anamnesis, physical examination, and otorhinolaryngologic exam. The patients had cutaneous test for mites before and after 1 year of sublingual specific immunotherapy. The cutaneous response was classified as negative (absent), light, moderate, or severe. Results  Before vaccination, 42 (40.4%) patients were classified as having a severe form of allergy and 62 (59.6%) as having a moderate allergy. After the specific therapy, 40 (38.4%) patients were classified as negative (absent), 37 (35.6%) as light, 19 (18.3%) as moderate, and 8 (7.7%) as severe responses. Conclusion  Immunotherapy, a desensitization technique, is indicated in cases which patients cannot avoid the exposure to allergens and in situations where pharmacologic therapy is not ideal. Specific immunotherapy to treat the allergic rhinitis in elderly patients was efficient and had no collateral effects...

‣ Epicutaneous Immunotherapy for Aeroallergen and Food Allergy

Senti, Gabriela; von Moos, Seraina; Kündig, Thomas M.
Fonte: Springer International Publishing Publicador: Springer International Publishing
Tipo: Artigo de Revista Científica
Português
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IgE-mediated allergies today affect up to 30 % of the population in industrialized countries. Allergen immunotherapy is the only disease-modifying treatment option with a long-term effect. However, very few patients (<5 %) choose immunotherapy, due to the long treatment duration (between 3–5 years) and possible local and systemic allergic side effects of the allergen administrations. The latter occur when an allergen accidentally reaches the blood circulation. Therefore, the ideal application route for allergen immunotherapy should be characterized by two hallmarks: firstly, by a high number of potent antigen-presenting cells, which enhance efficacy and thus shorten treatment duration. Secondly, the allergen administration site is ideally non-vascularized, so that inadvertent systemic distribution of the allergen and consequent systemic allergic side effects are minimized. The epidermis contains high numbers of potent antigen-presenting Langerhans cells and, as an epithelium, is non-vascularized. Therefore, the epidermis represents an interesting administration route. Historical evidence for the clinical efficacy of epicutaneous allergy immunotherapy (EPIT) has now been strengthened by a number of recent double-blinded placebo-controlled clinical trials performed by independent groups. We review the immunological rationale...

‣ Allergen Peptides, Recombinant Allergens and Hypoallergens for Allergen-Specific Immunotherapy

Marth, Katharina; Focke-Tejkl, Margarete; Lupinek, Christian; Valenta, Rudolf; Niederberger, Verena
Fonte: Springer International Publishing Publicador: Springer International Publishing
Tipo: Artigo de Revista Científica
Português
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Allergic diseases are among the most common health issues worldwide. Specific immunotherapy has remained the only disease-modifying treatment, but it is not effective in all patients and may cause side effects. Over the last 25 years, allergen molecules from most prevalent allergen sources have been isolated and produced as recombinant proteins. Not only are these molecules useful in improved allergy diagnosis, but they also have the potential to revolutionize the treatment of allergic disease by means of immunotherapy. Panels of unmodified recombinant allergens have already been shown to effectively replace natural allergen extracts in therapy. Through genetic engineering, several molecules have been designed with modified immunological properties. Hypoallergens have been produced that have reduced IgE binding capacity but retained T cell reactivity and T cell peptides which stimulate allergen-specific T cells, and these have already been investigated in clinical trials. New vaccines have been recently created with both reduced IgE and T cell reactivity but retained ability to induce protective allergen-specific IgG antibodies. The latter approach works by fusing per se non-IgE reactive peptides derived from IgE binding sites of the allergens to a virus protein...

‣ Is The Allergen Really Needed in Allergy Immunotherapy?

Kündig, Thomas M.; Klimek, Ludger; Schendzielorz, Philipp; Renner, Wolfgang A.; Senti, Gabriela; Bachmann, Martin F.
Fonte: Springer International Publishing Publicador: Springer International Publishing
Tipo: Artigo de Revista Científica
Português
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Immunotherapy for type I allergies is well established and is regarded to be the most efficient treatment option besides allergen avoidance. As of today, different forms of allergen preparations are used in this regard, as well as different routes of application. Virus-like particles (VLPs) represent a potent vaccine platform with proven immunogenicity and clinical efficacy. The addition of toll-like receptor ligands and/or depot-forming adjuvants further enhances activation of innate as well as adaptive immune responses. CpG motifs represent intensively investigated and potent direct stimulators of plasmacytoid dendritic cells and B cells, while T cell responses are enhanced indirectly through increased antigen presentation and cytokine release. This article will focus on the function of VLPs loaded with DNA rich in nonmethylated CG motifs (CpGs) and the clinical experience gained in the treatment of allergic rhinitis, demonstrating clinical efficacy also if administered without allergens. Several published studies have demonstrated a beneficial impact on allergic symptoms by treatment with CpG-loaded VLPs. Subcutaneous injection of VLPs loaded with CpGs was tested with or without the adjuvant alum in the presence or absence of an allergen. The results encourage further investigation of VLPs and CpG motifs in immunotherapy...

‣ Adjuvant immunotherapy of patients with high-risk melanoma using vaccinia viral lysates of melanoma: Results of a randomized trial

Hersey, P.; Coates, A.; McCarthy, W.; Thompson, J.; Sillar, R.; McLeod, R.; Gill, P.; Coventry, B.; McMullen, A.; Dillon, H.; Simes, R.
Fonte: Amer Soc Clinical Oncology Publicador: Amer Soc Clinical Oncology
Tipo: Artigo de Revista Científica
Publicado em //2002 Português
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PURPOSE: Patients with high-risk melanoma treated by immunotherapy with vaccinia viral lysates were found in phase II studies to have improved survival compared with historical controls. We therefore elected to test this therapy in a phase III study. PATIENTS AND METHODS: A prospective, randomized, multicenter trial to determine whether immunotherapy with a vaccine prepared from vaccinia melanoma cell lysates (VMCL) over a 2-year period after definitive surgery would improve relapse-free survival (RFS) and overall survival (OS) in patients with American Joint Committee on Cancer stage IIB and III melanoma compared with a control group treated only with surgery. RESULTS: A total of 700 patients were randomized: 353 to VMCL and 347 to no immunotherapy. Seventy-seven percent had lymph node (LN) metastases and 66% had clinically detected LN metastases. Analysis on the basis of all eligible, randomized patients (n = 675) found, after a median follow-up period of 8 years, a median OS of 88 months in the control versus 151 months in the treated group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.64 to 1.02; P = .068 by stratified univariate Cox analysis). At 5 and 10 years, survival rates for control and treated patients were 54.8% v 60.6% and 41% v 53.4%...

‣ Untersuchung des basophilen Aktivationsmarkers Ectonukleotid Pyrophosphatase/Phosphodiesterase 3 (E-NPP3) als Verlaufsparameter der spezifischen Hyposensibilisierung bei Patienten mit Insektengiftallergie; Monitoring the basophil-specific ectoenzyme E-NPP3 (CD203c) as progress parameter of a specific immunotherapy of patients allergic to hymenoptera venom.

Hüttig, Fabian
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
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1.1 Einleitung Die allergische Reaktion auf den Stich eines Hautflüglers (Hymenopter) kann für 3-5% der mitteleuropäischen Bevölkerung eine lebensbedrohliche Situation darstellen. Eine spezifische Immuntherapie ermöglicht es Patienten erfolgreich zu hyposensibilisieren. Die Erfolgskontrolle dieser Behandlung, ist momentan nur durch eine sog. Stichprovokation möglich. Unklarheiten im Funktionsmechanismus der Hyposensibilisierung machen eine Prüfung des Therapieerfolgs mit einem verlässlichen Laborparameter nicht möglich. Die für Allergiker spezifische CD 203c-Expression auf basophilen Granulozyten ist ein Diagnostikum mit hoher Sensitivität und Spezifität. Eine Veränderung der Expression im Laufe einer spezifischen Immuntherapie wurde untersucht um mögliche Zusammenhänge zum Behandlungsergebnis darzustellen. 1.2 Patienten, Materialien und Methoden Bei 17 Patienten, die sich einer Hyposensibilisierungsbehandlung an der Universitätshautklinik unterzogen, wurde vor und nach der initialen Therapie (Rush-Schema) - sowie nach 16-33 Monaten Erhaltungstherapie die Expression des basophilen Aktiviationsmarkers CD203c untersucht. Es erfolgte eine Stimulation der Zellen mit Wespengift und Bienengift sowie mit PBS als Negativkontrolle und mit dem Anti-IgE-Antikörper DEpsilon2 als Positivkontrolle. Die Oberfläche wurde fluorochrommarkiert mit dem spezifischen monoklonalen Antikörper (97A6-PE) flowcytometrisch analysiert. Mediane Fluoreszenzintensitäten dienten zur Berechnung eines relativen Stimulationsindex...

‣ Computational Immunology : from MHC-peptide Binding to Immunotherapy; Computational Immunology : von MHC-Peptid Bindung zur Immuntherapie

Dönnes, Pierre
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
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The human immune system provides effective protection against invading pathogens and cancer. Soluble antibodies can directly bind to extracellular antigens, whereas other mechanisms are needed for the recognition of virally infected or cancerous cells. Intracellular proteins are digested into smaller peptides, which are then displayed on the cell surface bound to major histocompatibility (MHC) class I molecules. Cytotoxic T (Tc) cells play an important role in the immune system since they can recognize MHC-peptide complexes and eliminate infected or abnormal cells. The intracellular events leading to MHC-peptide presentation are collectively known as antigen processing. There are three main steps in the antigen processing pathway; digestion of proteins into peptides by proteasomes in the cytosol, transport of peptides into the endoplasmic reticulum (ER) by the transporters associated with antigen processing (TAP), and MHC-peptide complex formation. A detailed understanding of these processes is a prerequisite for rational peptide vaccine design aiming to efficiently activate Tc cells. This has motivated the development of computational methods dealing with the different steps of the antigen processing pathway. Methods predicting MHC-peptide binding with relatively good accuracy exists...

‣ Advances of MUC1 as a target for breast cancer immunotherapy

Yang, E.; Hu, X.F.; Xing, P.X.
Fonte: Murcia : F. Hernández Publicador: Murcia : F. Hernández
Tipo: Artigo de Revista Científica Formato: application/pdf
Português
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MUC1 is a potential target in breast cancer immunotherapy as MUC1 is overexpressed in breast cancer, and is absent or expressed in low level in normal mammary gland. In addition, MUC1 is mostly aberrantly underglycosylated in cancer and the antigens on the cancer surface are different from normal cell. Therefore targeting MUC1 for cancer immunotherapy can exploit the difference between cancer and normal cells, and eliminating the cancerous cells while leaving the normal mammary cells unharmed. This review will focus on the recent advance of MUC1 breast cancer immunotherapy currently being investigated.

‣ Regression of melanoma metastases after immunotherapy is associated with activation of antigen presentation and interferon-mediated rejection genes

Carretero Coca, Rafael; Wang, Ena; Rodr??guez, Ana I.; Reinboth, Jennifer; Ascierto, Mar??a L.; Engle, Alyson M.; Liu, Hui; Camacho, Francisco M.; Marincola, Francesco M.; Garrido Torres-Puchol, Federico; Cabrera Castillo, Mar??a Teresa
Fonte: International Union against Cancer (UICC) Publicador: International Union against Cancer (UICC)
Tipo: Pré-impressão
Português
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We present the results of a comparative gene expression analysis of 15 metastases (10 regressing and 5 progressing) obtained from 2 melanoma patients with mixed response following different forms of immunotherapy. Whole genome transcriptional analysis clearly indicate that regression of melanoma metastases is due to an acute immune rejection mediated by the upregulation of genes involved in antigen presentation and interferon mediated response (STAT-1/IRF-1) in all the regressing metastases from both patients. In contrast, progressing metastases showed low transcription levels of genes involved in these pathways. Histological analysis showed T cells and HLA-DR positive infiltrating cells in the regressing but not in the progressing metastases. Quantitative expression analysis of HLA-A,B and C genes on microdisected tumoral regions indicate higher HLA expression in regressing than in progressing metastases. The molecular signature obtained in melanoma rejection appeared to be similar to that observed in other forms of immune-mediated tissue-specific rejection such as allograft, pathogen clearance, graft versus host or autoimmune disease, supporting the immunological constant of rejection. We favor the idea that the major factor determining the success or failure of immunotherapy is the nature of HLA Class I alterations in tumor cells and not the type of immunotherapy used. If the molecular alteration is reversible by the immunotherapy...

‣ Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy

Lima, Luís; Severino, Paulo; Silva, Mariana; Miranda, Andreia; Tavares, Ana; Pereira, Sofia; Fernandes, Elisabete; Cruz, Ricardo; Amaro, Teresina; Reis, Celso; Dall'Olio, Fabio; Amado, Francisco; Videira, Paula; Santos, Lúcio; Ferreira, José Alexandre
Fonte: Cancer Research UK Publicador: Cancer Research UK
Tipo: Artigo de Revista Científica
Publicado em //2013 Português
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High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of this work is to determine the efficiency of BCG immunotherapy against tumours expressing sTn and sTn-related antigen sialyl-6-T (s6T). METHODS: In a retrospective design, 94 tumours from patients treated with BCG were screened for sTn and s6T expression. In vitro studies were conducted to determine the interaction of BCG with high-grade bladder cancer cell line overexpressing sTn. RESULTS: From the 94 cases evaluated, 36 had recurrence after BCG treatment (38.3%). Treatment outcome was influenced by age over 65 years (HR=2.668; (1.344-5.254); P=0.005), maintenance schedule (HR=0.480; (0.246-0.936); P=0.031) and multifocality (HR=2.065; (1.033-4.126); P=0.040). sTn or s6T expression was associated with BCG response (P=0.024; P<0.0001) and with increased recurrence-free survival (P=0.001). Multivariate analyses showed that sTn and/or s6T were independent predictive markers of recurrence after BCG immunotherapy (HR=0.296; (0.148-0.594); P=0.001). In vitro studies demonstrated higher adhesion and internalisation of the bacillus to cells expressing sTn...

‣ Immunotherapy of Cytotoxic T Cell-resistant Tumors by T Helper 2 Cells: An Exotaxin and STAT6-dependent Process

Mattes, Joerg; Hulett, Mark; Xie, Wei; Hogan, Simon; Rothenberg, Marc E; Foster, Paul S; Parish, Christopher
Fonte: Rockefeller University Press Publicador: Rockefeller University Press
Tipo: Artigo de Revista Científica
Português
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Currently most attempts at cancer immunotherapy involve the generation of CD8+ cytotoxic T lymphocytes (CTLs) against tumor-associated antigens. Many tumors, however, have been immunoselected to evade recognition by CTLs and thus alternative approaches to cancer immunotherapy are urgently needed. Here we demonstrate that CD4+ T cells that recognize a secreted tumor-specific antigen and exhibit a cytokine secretion profile characteristic of Th2 cells, are capable of clearing established lung and visceral metastases of a CTL-resistant melanoma. Clearance of lung metastases by the Th2 cells was found to be totally dependent on the eosinophil chemokine, eotaxin, and partially dependent on the transcription activator signal transducer and activator of transcription 6 (STAT6), with degranulating eosinophils within the tumors inducing tumor regression. In contrast, tumor-specific CD4+ Th1 cells, that recruited macrophages into the tumors, had no effect on tumor growth. This work provides the basis for a new approach to adoptive T cell immunotherapy of cancer.

‣ Cancer immunotherapy: The past, the present and the future

Parish, Christopher
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
Português
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One of the most controversial issues in immunology for over a century has been whether an effective immune response can be elicited against malignant tumours. Whether the immunology community has believed cancer immunotherapy is feasible or impossible has been largely determined by the prevailing immunological paradigms at that time. In fact, during the last 110 years it is possible to trace at least five dramatic fluctuations in attitude towards cancer immunotherapy. It now appears, however, that overwhelming evidence is available to support the view that both the innate and adaptive immune responses can recognize and eliminate tumours. On the other hand, it remains to be seen if these immune responses can be harnessed to control cancer as, at the time of diagnosis, many tumours have already been immunoselected to be highly resistant to immune elimination. Based on these observations it is argued that immunotherapy approaches, other than the generation of tumour-specific cytotoxic T lymphocytes, must be explored. Alternative strategies include recruiting tumouricidal myeloid cells into tumours, generating antiangiogenic immune responses and directing innate immunity to hypoxia-induced ligands on tumour cells.