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1.
Br J Haematol ; 204(2): 525-533, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37905734

RESUMO

Varnimcabtagene autoleucel (var-cel) is an academic anti-CD19 chimeric antigen receptor (CAR) product used for the treatment of non-Hodgkin lymphoma (NHL) in the CART19-BE-01 trial. Here we report updated outcomes of patients with NHL treated with var-cel. B-cell recovery was compared with patients with acute lymphoblastic leukaemia (ALL). Forty-five patients with NHL were treated. Cytokine release syndrome (any grade) occurred in 84% of patients (4% grade ≥3) and neurotoxicity in 7% (2% grade ≥3). The objective response rate was 73% at Day +100, and the 3-year duration of response was 56%. The 3-year progression-free and overall survival were 40% and 52% respectively. High lactate dehydrogenase was the only covariate with an impact on progression-free survival. The 3-year incidence of B-cell recovery was lower in patients with NHL compared to ALL (25% vs. 60%). In conclusion, in patients with NHL, the toxicity of var-cel was manageable, while B-cell recovery was significantly prolonged compared to ALL. This trial was registered as NCT03144583.


Assuntos
Linfoma de Células B , Linfoma não Hodgkin , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Linfoma de Células B/terapia , Linfoma não Hodgkin/terapia , Imunoterapia Adotiva/efeitos adversos , Anticorpos , Antígenos CD19 , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfócitos T
2.
Clin Chim Acta ; 460: 78-87, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27350293

RESUMO

After decades of progress based on chemotherapy and targeted agents, patients with metastatic colorectal cancer still have low long-term survival, with more than 500,000 deaths occurring worldwide every year. Recent results showing clinical evidence of efficacy using immunotherapy in other types of tumors, such as melanoma and lung cancer, have also made this a viable therapy for evaluation in colorectal cancer in clinical trials. The development of cancer immunotherapies is progressing quickly, with a variety of technological approaches. This review summarizes the current status of clinical trials testing immunotherapy in colorectal cancer and discusses what has been learned based on previous results. Immunotherapy strategies, such as various models of vaccines, effector-cell therapy and checkpoint inhibitor antibodies, provide protection against progression for a limited subset of patients diagnosed with colorectal cancer. A better understanding of particular immune cell types and pathways in each patient is still needed. These findings will enable the development of novel biomarkers to select the appropriate subset of patients to be treated with a particular immunotherapy, and the tendencies determined from recent results can guide clinical practice for oncologists in this new therapeutic area and in the design of the next round of clinical trials.


Assuntos
Neoplasias Colorretais/terapia , Imunoterapia/métodos , Ensaios Clínicos como Assunto , Humanos , Medicina de Precisão
3.
Pancreas ; 44(7): 1078-82, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26335011

RESUMO

OBJECTIVES: Several serological markers have been reported in autoimmune pancreatitis (AIP) patients. However, only serum IgG4 (sIgG4) is available in clinical practice for AIP diagnosis. Antiamylase α antibodies (AMY-α Abs) have been proposed to diagnose AIP. This study evaluates the utility of AMY-α Abs and sIgG4 for AIP diagnosis. METHODS: Twenty-five AIP patients, 84 disease control groups (31 chronic pancreatitis, 30 acute pancreatitis, 23 pancreatic adenocarcinoma), and 59 healthy donors were prospectively studied. The AMY-α Abs were determined by homemade enzyme-linked immunosorbent assay and sIgG4 by nephelometry. RESULTS: Increased sIgG4 were detected to be present in 52% of AIP, 5% in control groups, and 0% in healthy donors, and AMY-α Abs, respectively, in 76%, 36%, and 2%. sIgG4 was elevated in 92% of the 13 patients with type 1 AIP, but in none of 3 with type 2 and of 8 with not otherwise specified AIP. The AMY-α Abs were present in 79%, 67%, and 75% of type 1, type 2, and not otherwise specified AIP, respectively. Sensitivity and specificity of AMY-α Abs were 76% and 78%, and of sIgG4 50% and 94%. By combining the 2 serological markers, sensitivity was 41%, and specificity was 99%. CONCLUSIONS: The AMY-α Abs may help to diagnosis of AIP and to differentiate AIP subtypes.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/sangue , Biomarcadores/sangue , alfa-Amilases Pancreáticas/imunologia , Pancreatite/sangue , Doença Aguda , Adolescente , Adulto , Idoso , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/imunologia , Pancreatite/diagnóstico , Pancreatite/imunologia , Pancreatite Crônica/sangue , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/imunologia , Sensibilidade e Especificidade , Adulto Jovem , Neoplasias Pancreáticas
4.
Immunol Res ; 61(1-2): 141-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25424577

RESUMO

Vitamin D immune-modulating effects were extensively studied, and low levels have been linked with autoimmune diseases. The associations of vitamin D with autoimmune diseases of the liver, and particularly primary biliary cirrhosis (PBC), are yet to be defined. Hence, in this study, serum levels of vitamin D were determined in 79 patients with PBC and 70 age- and sex-matched controls by the LIAISON chemiluminescent immunoassays (DiaSorin-Italy). Clinical and serological parameters of patients were analyzed with respect to vitamin D status. Mean levels of vitamin D were significantly lower among patients with PBC compared with controls (16.8 ± 9 vs. 22.1 ± 9 ng/ml; p = 0.029), and vitamin D deficiency (≤10 ng/ml) was documented in 33% of patients with PBC versus 7% of controls (p < 0.0001). Vitamin D levels inversely correlated with advanced liver damage and the presence of concomitant autoimmune diseases. In contrast, higher levels of vitamin D were observed among patients with PBC treated with ursodeoxycholic acid (UDCA). In conclusion, low vitamin D levels are common among patients with PBC and correlate with advanced disease, lack of UDCA therapy and autoimmune comorbidity. This alludes to the plausible roles of vitamin D as a prognostic marker of PBC severity, and as a potential player in this disease pathogenesis. While further studies are awaited, monitoring vitamin D in patients with PBC and use of supplements may be advisable.


Assuntos
Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/diagnóstico , Vitamina D/sangue , Idoso , Autoimunidade , Biomarcadores/sangue , Biópsia , Estudos de Casos e Controles , Feminino , Humanos , Fígado/imunologia , Fígado/patologia , Cirrose Hepática Biliar/etiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Deficiência de Vitamina D/complicações
5.
Autoimmun Rev ; 9(4): 237-40, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19622398

RESUMO

Since Sarles et al. [Sarles H, Sarles JC, Muratore R, Guien C. Chronic inflammatory sclerosis of the pancreas-an autonomous pancreatic disease? Am J Dig Dis 1961; 6: 688-698.] reported a case of pancreatitis associated with hypergammaglobulinemia, many cases have been described, which led to the current concept of "autoimmune pancreatitis (AIP)". Lymphoplasmacytic infiltration and fibrosis on histology together with elevated IgG levels or the presence of autoantibodies on laboratory examinations supported the concept of AIP. In recent years, based on histological and immunohistochemical examination of various organs of patients with AIP, a novel clinicopathological entity, IgG4-related slerosing disease, has been proposed. AIP is a systemic disease that is characterized by dense infiltration of IgG4-positive plasma cells and T lymphocytes in various organs. Clinical manifestations are related with pancreas dysfunction but other organs may be affected such as bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung and prostate. Increased serum IgG4 levels, the presence of several autoantibodies such as anti-carbonic anhydrase II antibodies (ACA-II), immunostaining IgG4 positive in pancreas tissue and a very good response to steroid therapy are useful for the diagnosis of AIP that can mimic pancreatic cancer.


Assuntos
Doenças Autoimunes/diagnóstico , Anidrases Carbônicas/imunologia , Neoplasias Pancreáticas/diagnóstico , Pancreatite/diagnóstico , Pancreatite/imunologia , Autoanticorpos/sangue , Doenças Autoimunes/imunologia , Doenças Autoimunes/fisiopatologia , Biomarcadores/sangue , Movimento Celular , Diagnóstico Diferencial , Fibrose , Humanos , Hipergamaglobulinemia , Imunoglobulina G/sangue , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/fisiopatologia , Pancreatite/fisiopatologia , Plasmócitos/imunologia , Guias de Prática Clínica como Assunto , Linfócitos T/imunologia
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