Blinatumomabe para leucemia linfoblástica aguda (LLA) B derivada pediátrica em primeira recidiva medular de alto risco / Blinatumomab for pediatric B-derived acute lymphoblastic leukemia (ALL) in first high-risk spinal cord relapse

INTRODUÇÃO: A leucemia linfoblástica aguda (LLA) pediátrica é uma neoplasia maligna agressiva e heterogênea caracterizada pela proliferação clonal e acúmulo de linfoblastos na medula óssea e sangue periférico. Entre os pacientes pediátricos, mais de 95% atingem remissão completa após o primeiro tratamento e 75% a 85% permanecem livre de doença por cinco anos após o diagnóstico. Porcentagens de 15% a 20% sofrem recidiva que são classificadas em risco padrão (RP) ou alto risco (AR). Em crianças com primeira recidiva medular de alto risco a sobrevida global é de 20%. A recidiva após o tratamento inicial é a segunda maior causa de mortalidade relacionada ao câncer em crianças. Crianças que apresentam recidiva de alto risco ao tratamento inicial são candidatas ao transplante de células hematopoiéticas após atingirem uma segunda remissão completa, entretanto, as chances de remissão diminuem significativamente entre a primeira, segunda e terceiras recidivas. Nessa população, a presença de doença residual

Bispecific antibodies in clinical tumor therapy / 生物工程学报

Bispecific antibody (BsAb) has two different antigen-binding sites, divided into the "IgG-like" format and the "non-IgG-like" format. Different formats have different characteristics and applications. BsAb has higher sensitivity and specificity than conventional antibodies, with special functions such as recruitment of immune cells and blocking of dual signaling pathways, playing an important role in immune-diagnosis and therapy. With the deterioration of the global environment and the irregular living habits of people, the incidence of tumor is becoming higher and higher. Tumor becomes the most serious fatal disease threatening human health after cardiovascular disease. There are 12 million estimated new tumor cases each year worldwide. The major clinical treatments of tumor are surgical resection, chemoradiotherapy, target therapy. Tumor immunotherapy is a novel approach for tumor treatment in recent years, and activates human immune system to control and kill tumor cells. Although the traditional monoclonal antibodies have already acquired some therapeutic effects in tumor targeted therapy and immunotherapy, they induce drug resistance resulted from the heterogeneity and plasticity of tumors. Binding to two target antigens at the same time, BsAb has been used in the clinical treatment of tumors and obtained promising outcomes. This review elaborates the research progress and applications of bispecific antibody in clinical tumor therapy.

Emerging immunological strategies: recent advances and future directions / 医学前沿

Immunotherapy plays a compelling role in cancer treatment and has already made remarkable progress. However, many patients receiving immune checkpoint inhibitors fail to achieve clinical benefits, and the response rates vary among tumor types. New approaches that promote anti-tumor immunity have recently been developed, such as small molecules, bispecific antibodies, chimeric antigen receptor T cell products, and cancer vaccines. Small molecule drugs include agonists and inhibitors that can reach the intracellular or extracellular targets of immune cells participating in innate or adaptive immune pathways. Bispecific antibodies, which bind two different antigens or one antigen with two different epitopes, are of great interest. Chimeric antigen receptor T cell products and cancer vaccines have also been investigated. This review explores the recent progress and challenges of different forms of immunotherapy agents and provides an insight into future immunotherapeutic strategies.

Primera experiencia de tratamiento con emicizumab en un paciente con hemofilia A severa e inhibidor de alto título en Uruguay / First report of emicizumab use in a patient with severe haemophilia A and high-titer inhibitor in Uruguay / Primeira experiência de tratamento com emicizumab em paciente com hemofilia A grave e inibidor de alto título no Uruguai

La hemofilia A es una coagulopatía congénita causada por la deficiencia o el mal funcionamiento del factor VIII de la coagulación. Una de las complicaciones más graves del tratamiento de la hemofilia A es el desarrollo de inhibidores que hacen que la terapia de reemplazo con FVIII sea ineficaz, dificultando la prevención y el control de los sangrados. El emicizumab es un anticuerpo monoclonal humanizado biespecífico dirigido contra los factores FIXa y FX, que imita la función de cofactor del FVIII. El tratamiento profiláctico con emicizumab es seguro y eficaz para prevenir hemorragias en los pacientes con hemofilia A con y sin inhibidores. Se presenta el caso del primer paciente tratado con emicizumab en Uruguay.

Haemophilia A is a congenital coagulopathy caused by a deficiency or malfunction of coagulation factor VIII. One of the most serious complications of haemophilia A treatment is the development of inhibitors that render FVIII replacement therapy ineffective, making it difficult to prevent and control bleeding. Emicizumab is a humanized bispecific monoclonal antibody directed against factors FIXa and FX, which mimics the cofactor function of FVIII. Emicizumab has been shown to be safe and effective as prophylaxis to prevent bleeding in haemophilia A patients with or without inhibitors to FVIII. We report the first patient treated with emicizumab in Uruguay.

A hemofilia A é uma coagulopatia congênita que se caracteriza pela ausência ou mau funcionamento do factor VIII da coagulação. Uma das complicações mais sérias do tratamento da hemofilia A é o desenvolvimento de inibidores que tornam a terapia de reposição do FVIII ineficaz, dificultando a prevenção e o controle do sangramento. O emicizumab é um anticorpo monoclonal biespecífico humanizado dirigido contra os fatores FIXa e FX, que imita a função de cofator do FVIII. O tratamento profilático com emicizumab é seguro e eficaz na prevenção de sangramento em pacientes com hemofilia A com e sem inibidores. É apresentado o caso do primeiro paciente tratado com emicizumabe no Uruguai.