Navegando por Palavras-chave "Immunotherapy"
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- ItemSomente MetadadadosAtividade fagocÍtica de monócitos em pacientes com carcinoma, antes e após imunoterapia com glucana(Universidade Federal de São Paulo (UNIFESP), 1984) Taketomi, Ernesto Akio [UNIFESP]; Mendes, Nelson Figueiredo [UNIFESP]
- ItemAcesso aberto (Open Access)Avaliação do uso combinado da imunização ativa com MAB 10.D7 e passiva com MAB 3F12E7 em modelo de melanoma murino B16F10(Universidade Federal de São Paulo (UNIFESP), 2019-04-25) Hamaguchi, Barbara [UNIFESP]; Moraes, Jane Zveiter De [UNIFESP]; http://lattes.cnpq.br/6568232956872184; http://lattes.cnpq.br/0443667340525603; Universidade Federal de São Paulo (UNIFESP)Melanoma is an aggressive and lethal type of cancer which requires new approaches to be effectively treated. Angiogenesis-directed immunotherapy may contribute to refrain tumoral growth and metastization. Our group has successfully developed two monoclonal antibodies (mAb): 3F12E7, which recognizes fibroblast growth factor 2 (FGF2), and 10.D7 that interferes with vascular endothelial growth factor (VEGF) activity, both showing promising results in combating tumoral development. Objective: To verify the existence of combining effects in combining both mAbs over B16F10 tumor growth inhibition. Methods: Groups of C57Bl/6 mice were actively immunized twice with a sevenday interval with either mAb 10.D7 or irrelevant mAb conjugated with KLH. Ten days after the second immunization, mice were subcutaneously inoculated with B16F10 cells. Thereafter, mice were treated with either mAb 3F12E7 or irrelevant antibody by intraperitoneal injection, for five consecutive times every 48 hours. The animals had their sera collected for evaluation of VEGF-binding antibodies on immunization, inoculation and euthanasia days, and tumor volume was measured daily. After euthanasia, tumors were excised and histological sections evaluated for the presence of necrosis and CD31+ vessels. Results: Mice treated with 10.D7/3F12E7 presented the lowest tumoral volumes and greater delay on tumor establishment when compared to the other groups of treatments. Also, the smallest tumors were found in those animals with higher levels of VEGF-binding antibodies. Higher necrosis rates were observed in groups 10.D7/Irrelevant and 10.D7/3F12E7, which was inversely proportional to the presence of CD31+ vessels. Data were compared by means of one-way ANOVA test, p <0.05. Conclusion: There is a combined effect on the inhibition of tumor development when immunizations with mAbs 10.D7 and 3F12E7 are associated.
- ItemSomente MetadadadosBlockade of CTLA-4 promotes the development of effector CD8(+) T lymphocytes and the therapeutic effect of vaccination with an attenuated protozoan expressing NY-ESO-1(Springer, 2015-03-01) Santos, Luara Isabela dos; Galvao-Filho, Bruno; Faria, Paula Cristina de; Junqueira, Caroline; Dutra, Miriam Santos; Ribeiro Teixeira, Santuza Maria; Rodrigues, Mauricio Martins [UNIFESP]; Ritter, Gerd; Bannard, Oliver; Fearon, Douglas Thomas; Antonelli, Lis Ribeiro; Gazzinelli, Ricardo Tostes; Fundacao Oswaldo Cruz; Universidade Federal de Minas Gerais (UFMG); Universidade Federal de São Paulo (UNIFESP); Mem Sloan Kettering Canc Ctr; Univ Calif San Francisco; Univ Cambridge; Univ MassachusettsThe development of cancer immunotherapy has long been a challenge. Here, we report that prophylactic vaccination with a highly attenuated Trypanosoma cruzi strain expressing NY-ESO-1 (CL-14-NY-ESO-1) induces both effector memory and effector CD8(+) T lymphocytes that efficiently prevent tumor development. However, the therapeutic effect of such a vaccine is limited. We also demonstrate that blockade of Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) during vaccination enhances the frequency of NY-ESO-1-specific effector CD8(+) T cells producing IFN-gamma and promotes lymphocyte migration to the tumor infiltrate. As a result, therapy with CL-14-NY-ESO-1 together with anti-CTLA-4 is highly effective in controlling the development of an established melanoma.
- ItemSomente MetadadadosCost-effectiveness of immune checkpoint inhibitors in nsclc according to pd-l1 expression(Hindawi Ltd, 2016) Aguiar, Pedro, Jr. [UNIFESP]; Perry, Luke A.; Lopes, Gilberto L., Jr.
- ItemSomente MetadadadosEmprego de glucana em imunoterapia de pacientes com carcinoma: estudo da atividade fagocítica de monócitos e avaliacao in vivo da imunidade celular(Universidade Federal de São Paulo (UNIFESP), 1986) Taketomi, Ernesto Akio [UNIFESP]; Mendes, Nelson Figueiredo [UNIFESP]
- ItemSomente MetadadadosExploring the Role of Soluble Factors Associated with Immune Regulatory Properties of Mesenchymal Stem Cells(Humana Press Inc, 2012-06-01) Bassi, Enio Jose; Almeida, Danilo Candido de [UNIFESP]; Mendes Moraes-Vieira, Pedro Manoel; Saraiva Camara, Niels Olsen; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)Mesenchymal stem cells (MSCs) are characterized as multipotent stromal cells with the capacity for both self-renewal and differentiation into mesodermal cell lineages. MSCs also have a fibroblast-like phenotype and can be isolated from several tissues. in recent years, researchers have found that MSCs secrete several soluble factors that exert immunosuppressive effects by modulating both innate (macrophages, dendritic and NK cells) and adaptive (B cells and CD4+ and CD8+ T cells) immune responses. This review summarizes the principal trophic factors that are related to immune regulation and secreted by MSCs under both autoimmune and inflammatory conditions. the understanding of mechanisms that regulate immunity in MSCs field is important for their future use as a novel cellular-based immunotherapy with clinical applications in several diseases.
- ItemAcesso aberto (Open Access)Identificação, por anticorpo monoclonal, de proteína de 230 kDa relacionada com malignidade em melanoma murino(Universidade Federal de São Paulo (UNIFESP), 2006-12-31) Mendes, Priscila Fraga Penteado [UNIFESP]; Lopes, Jose Daniel [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Melanomas se destacam entre os tumores sólidos por apresentar alto potencial de malignidade e incidência crescente, especialmente entre indivíduos jovens. Identificação de marcadores moleculares em melanomas é de enorme interesse para uso clínico e para estudos relacionados ao seu desenvolvimento. A linhagem de melanoma murino B16 tem sido amplamente empregada visando melhor compreensão do processo metastático. Objetivo: identificar moléculas na superfície de células B16, empregando anticorpos monoclonais, que apresentem função biológica importante para essas células, bem como investigar expressão de moléculas reconhecidas pelos mesmos mAbs em melanoma humano. Métodos: camundongos C57Bl/6 foram imunizados com células B16 irradiadas para produção de híbridos produtores de mAb. Resultados: após fusão foi obtido mAb da classe IgM, designado G12F2, que reconheceu uma única banda de aproximadamente 230 kDa em extrato total de células B16. A molécula era expressa na superfície celular e não por células não tumorigênicas, como fibroblastos ou melanócitos melan-a. Células não tumorigênicas, derivadas de melan-a, também não a expressaram ao passo que células tumorigênicas, de mesma origem, expressaram-na em grande quantidade. Variante menos metastática da linhagem B16 expressou menor quantidade desta molécula quando comparado à variante mais metastática. A neutralização da molécula de 230 kDa com mAb G12F2 inibiu proliferação, migração e invasão por células B16 in vitro. Também nestas condições, G12F2 promoveu atividade citolítica contra células B16, mediada por complemento. Por outro lado, adição in vitro de mAb G12F2 em nada alterou adesão das células B16 à fibronectina e laminina, ou adesão célula-célula. In vivo, o tratamento com mAb G12F2 inibiu crescimento do nódulo tumoral e formação de metástases pulmonares. Quando testado contra extrato de tumores de origem humana, como carcinoma e melanoma, mAb G12F2 reconheceu banda de 75 e 67 kDa, respectivamente. Por fim, foi demonstrado que mAb inibiu proliferação de células de melanoma humano in vitro. Conclusões: a molécula de 230 KDa parece ter importância durante crescimento do melanoma murino; identificação de molécula homóloga em melanoma humano fornecerá subsídios para diagnóstico e protocolos visando imunoterapia.
- ItemSomente MetadadadosPotencialidades do anticorpo anti-ID de Bevacizumabe 10.D7 que mimetiza VEGF(Universidade Federal de São Paulo (UNIFESP), 2021) Silva, Tabata De Almeida Da [UNIFESP]; Moraes, Jane Zveiter De [UNIFESP]; Universidade Federal de São PauloBevacizumab is a humanized monoclonal antibody (mAb) against vascular endothelial growth factor (VEGF), which plays an essential role in the tumor angiogenic process. The antibody is approved for use in the treatment of several tumors, but it causes adverse effects that sometimes make its use unfeasible. In previous work, our group developed an anti-bevacizumab idiotype (Id) antibody, mAb 10.D7, and showed promising results in response to its use as an immunogen (Sanches et al. 2016). The present study explores the potential of mAb 10.D7 in a B16F10 murine melanoma model. The effects of mAb 10.D7 in inhibiting metastasis formation, in association with a chemotherapy agent and as a gene vaccine were evaluated. The results show that animals immunized with mAb 10.D7 exhibit a reduction in the formation of metastatic nodules and an additive effect occurs when immunotherapy is combined with chemotherapy. To assess the use of anti-Id antibody as a gene vaccine, two versions of single-chain variable fragments (single-chain variable fragment, scFv) were constructed. The light (FvL) and heavy (FvH) chain variable region genes were isolated from mAb 10.D7-secreting hybridoma cells and the gene fragments were joined by a linker following two orientations: FvLàFvH and FvHàFvL. Constructs were synthesized and cloned into mammalian cell expression vector. The plasmids carrying the genes of interest were used as an immunogen in mice, which responded by making VEGF-binding anti-anti-Id antibodies. Animals immunized with the plasmid carrying the scFv 10.D7 gene under the FvHàFvL orientation, when challenged with melanoma cells, showed delay in tumor growth, data that point to the feasibility of using the approach as an anti-angiogenic gene immunotherapy.
- ItemSomente MetadadadosRapid Eye Movement Sleep Behavior Disorder in Paraneoplastic Cerebellar Degeneration: Improvement with Immunotherapy(Amer Acad Sleep Medicine, 2016) Vale, Thiago Cardoso; Prado, Lucila Bizari Fernandes do [UNIFESP]; Prado, Gilmar Fernandes do [UNIFESP]; Barsottini, Orlando Graziani Povoas [UNIFESP]; Pedroso, Jose Luiz [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Study Objectives: To report two female patients with paraneoplastic cerebellar degeneration (PCD) related to breast cancer that presented with rapid eye movement-sleep behavior disorder (RBD) and improved sleep symptoms with immunotherapy. Methods: The two patients were evaluated through clinical scale and polysomnography before and after therapy with intravenous immunoglobulin. Results: RBD was successfully treated with immunotherapy in both patients. Score on the RBD screening questionnaire dropped from 10 to 1 or 0, allied with the normalization of polysomnographic findings. Conclusions: A marked improvement in RBD after immunotherapy in PCD raises the hypothesis that secondary RBD may be an immune-mediated sleep disorder.
- ItemAcesso aberto (Open Access)Síndrome da pessoa rígida: avaliação de 14 pacientes(Universidade Federal de São Paulo (UNIFESP), 2016-09-27) Lino, Valeria Cavalcante [UNIFESP]; Oliveira, Acary Souza Bulle [UNIFESP]; http://lattes.cnpq.br/3911841387107665; http://lattes.cnpq.br/0729750480900588; Universidade Federal de São Paulo (UNIFESP)Main objective: to describe the characteristics of patients with stiff person syndrome (SPS). Secundary: a) to evaluate clinical and laboratorial findings; b)to identify the best therapeutic responses; c) to identify prognostic factors. Methods: we reviewed medical records and included patients with diagnosis of SPS (January 1989 to May 2015) in Neuromuscular Diseases Section at the Federal University of São Paulo (Unifesp), which had at least: axial stiffness with or without limb involvement; episodic spasms superimposed on the underlying rigidity, precipitated by unexpected external stimuli (tactile stimuli, sudden noises, emotional upset) and absence of any other neurologic disease that could account for rigidity and spasms. This study was approved by the Committee for Ethic in Research of Unifesp and Free and Informed Consent was applied to contactable patients. Compiled data: demographic data; age at symptom onset; time to diagnosis; experts who evaluated the patient and respective diagnosis; examination findings; coexisting diseases, labor capacity.The spasms severity was evaluated based on at Penn scale and a level of disability diagnosis was assigned using the modified Rankin score (RS). Serological (GAD65 antibody), electrophysiological and neuraxial magnetic resonance (nMR) data at the time of initial evaluation were also assessed. Results: Fourteen patients (eight having Classic-SPS; four having Focal-SPS; and two having PLUS-SPS) were GAD65 antibody seropositive; 11 were female(3.6: 1); mean age at symptom onset: 42.57 years; time to diagnosis: on average 43.28 months (Classic-SPS: 46.75 months; Focal-SPS: 15.25 and PLUS-SPS: 85.5). Examination findings: facial hypomimia (28.57%); laryngeal spasms (28.6%); cognitive disorders (50%); increased patellar reflexes (71.43%); muscle stiffness, spasms superimposed on the underlying rigidity, co- contraction of agonist and antagonist muscles (100%); hyperlordosis (50%); impaired gait (100%); pain (78.6%); falls (64.3%); electromyography: involuntary continuous paraspinal motor unity activity (42.85%), co-contraction (28.57%); nMR changes: nodular changes in white matter?s brain (PLUS-SPS with ataxia, one case); accentuation of physiological lumbosacral curvature (two cases). Frequently coexisting diseases: autoimmune diseases: 64.3% (type I diabetes mellitus in 50% and autoimmune thyroid disease in 28.6%) and psychiatric disorders (78.6%). Pharmacologic treatment and the best outcomes: symptomatic benefits: were reported in patients (57,14%) treated with diazepam and baclofen (improvement of RS and subjective symptoms); immunotherapy: nine patients (90%) improved after combination of intravenous immune globulin (IVig) and symptomatic drugs (improvement of RS and subjective symptoms), one patient had improved RS after combination of Ivig and intravenous cyclophosphamide. Conclusion: the study emphasized clinical and laboratory data and has demonstrated the insidious and debilitating clinical evolution ofthis rare syndrome. Patients diagnosed and treated early had better outcomes (reduction of subjective symptoms of muscle stiffness, pain, spasms, andreduction of objective symptoms evaluated by RS). Patients who used diazepam, baclofen and IVig in high doses for longer than six months had betterresponses on motor symptoms.
- ItemSomente MetadadadosVaccination using melanoma cells treated with p19arf and interferon beta gene transfer in a mouse model: a novel combination for cancer immunotherapy(Springer, 2016) Medrano, Ruan Felipe Vieira; Catani, Joao Paulo Portela; Ribeiro, Aline Hunger; Tomaz, Samanta Lopes [UNIFESP]; Merkel, Christian A.; Costanzi-Strauss, Eugenia; Strauss, Bryan E.Previously, we combined p19(Arf) (Cdkn2a, tumor suppressor protein) and interferon beta (IFN-beta, immunomodulatory cytokine) gene transfer in order to enhance cell death in a murine model of melanoma. Here, we present evidence of the immune response induced when B16 cells succumbing to death due to treatment with p19(Arf) and IFN-beta are applied in vaccine models. Use of dying cells for prophylactic vaccination was investigated, identifying conditions for tumor-free survival. After combined p19(Arf) and IFN-beta treatment, we observed immune rejection at the vaccine site in immune competent and nude mice with normal NK activity, but not in NOD-SCID and dexamethasone immunosuppressed mice (NK deficient). Combined treatment induced IL-15, ULBP1, FAS/APO1 and KILLER/DR5 expression, providing a mechanism for NK activation. Prophylactic vaccination protected against tumor challenge, where markedly delayed progression and leukocyte infiltration were observed. Analysis of primed lymphocytes revealed secretion of TH1-related cytokines and depletion protocols showed that both CD4(+) and CD8(+) T lymphocytes are necessary for immune protection. However, application of this prophylactic vaccine where cells were treated either with IFN-beta alone or combined with p19(Arf) conferred similar immune protection and cytokine activation, yet only the combination was associated with increased overall survival. In a therapeutic vaccine protocol, only the combination was associated with reduced tumor progression. Our results indicate that by harnessing cell death in an immunogenic context, our p19(Arf) and IFN-beta combination offers a clear advantage when both genes are included in the vaccine and warrants further development as a novel immunotherapy for melanoma.