Terapia com células CAR-T: reprogramação celular para o combate de neoplasias malignas / CAR-T cell therapy: cell reprogramming to combat malignant neoplasms

As células CAR-T são linfócitos geneticamente modificados para reconhecerem um espectro amplo de antígenos de superfície celulares. Além disso, atacam células tumorais malignas, que expressam esses antígenos, por meio da ativação da coestimulação citoplasmática, secreção de citocinas, citólise de células tumorais e proliferação de células T. O objetivo desse estudo é abordar a imunoterapia com células CAR-T, a fim de explicar seu conceito, processo de fabricação e papel no tratamento de neoplasias hematológicas e tumores sólidos. Foi realizada uma revisão através do portal PubMed, utilizando como descritores: "car-t cell therapy" e "neoplasms", determinados com base nos "Descritores em Ciências da Saúde". Foram obtidos, inicialmente, 10 artigos, os quais foram lidos integralmente para a confecção dessa revisão. Além disso, foram adicionados 3 ensaios clínicos atualizados sobre o tema. Na terapia com células CAR-T, as células T são coletadas do paciente, geneticamente modificadas para incluir receptores de antígeno específicos e, posteriormente, expandidas em laboratórios e transfundidas de volta para o paciente. Assim, esses receptores podem reconhecer células tumorais que expressam um antígeno associado a um tumor. A terapia com células CAR-T é mais conhecida por seu papel no tratamento de malignidades hematológicas de células B, sendo a proteína CD19 o alvo antigênico mais bem estudado até o momento. Entretanto, estudos estão sendo feitos para verificar a eficácia desse tratamento, também, em tumores sólidos. Portanto, apesar de inicialmente ser indicada apenas para um grupo seleto de pessoas, essa terapia tem demonstrado grande potencial para atuar em um espectro maior de pacientes.

The CAR-T cells are lymphocytes genetically modified to recognize a broader spectrum of cell surface antigens. In addition, they attack malignant tumor cells, which express these antigens, by activating cytoplasmic co-stimulation, cytokine secretion, tumor cell cytolysis and T cell proliferation. The aim of this study is to address immunotherapy with CAR-T cells, in order to explain its concept, manufacturing process and role in the treatment of hematological neoplasms and solid tumors. This is a literature review conducted through the PubMed portal, that uses the terms "car-t cell therapy" and "neoplasms" as descriptors, determined based on the DeCS (Descritores em Ciências da Saúde). To prepare this review, initially 10 articles were found and read in full. In addition, 3 updated clinical trials on the subject were added. For CAR-T cell therapy, T cells are collected from the patient, genetically modified to include specific antigen receptors, and later expanded in laboratories and transfused back to the patient. Thus, these receptors can recognize tumor cells that express a tumor-associated antigen. CAR-T cell therapy is best known for its role in the treatment of B cell hematological malignancies, with the CD19 protein being the most studied antigenic target to date. However, studies are being conducted to verify the effectiveness of this treatment, also, in solid tumors. Therefore, despite being formulated only for a selected group of patients, this therapy has great potential to act on a broader spectrum of patients.

Expression of B7-related protein-1 on human coronary artery endothelial cells and its clinical significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of oxidized low density lipoprotein (ox-LDL) on the expression of B7-related protein-1 (B7RP-1) on human coronary artery endothelial cells (HCAECs).</p><p><b>METHODS</b>HCAECs were incubated in the presence of 100 mg/L ox-LDL for 24 h, and B7RP-1 expression levels were determined using fluorescence reverse transcription PCR (RT-PCR) and Western blotting.</p><p><b>RESULTS</b>B7RP-1 expression was detected HCAECs, with spots of fluorescence signals distributing on the cell membrane as observed under fluorescence microscope. RT-PCR with B7RP-1 specific primers yielded products of expected size (496 bp). Western blotting identified B7RP-1 expression in the HCAECs as a cell-associated protein with an apparent molecular mass of 70,000. Treatment of the cells with ox-LDL significantly increased B7RP-1 expression at both the mRNA and protein levels (P<0.05).</p><p><b>CONCLUSION</b>B7RP-1 is expressed on the membrane of HCAECs. ox-LDL can promote up-regulate the expression of B7RP-1, which might be one of the immunopathogenesis of atherosclerosis.</p>