Imunoterapia no câncer - inibidores do checkpoint imunológico / Immunotherapy and immune checkpoint inhibitors in cancer

O objetivo deste trabalho é fazer uma revisão atual do tratamento de alguns tipos de câncer com imunoterapia e inibidores do checkpoint imunológico. As fontes de dados incluíram artigos originais, revisões e publicações indexados nos bancos de dados PubMed, MEDLINE, LILACS, SciELO e publicações online nos últimos 20 anos. Os checkpoints imunológicos normalmente impedem o organismo de montar uma resposta imune contra células normais. Alguns tipos de câncer podem adquirir estes checkpoints de tal forma que estas células tumorais não são reconhecidas pelo sistema imune, e isto impede que ele seja ativado. A inibição dos checkpoints imunológicos pode melhorar a sobrevida de pacientes com malignidades avançadas. Isto inclui melanoma maligno, carcinoma renal, linfoma e câncer pulmonar de células não pequenas. Uma extraordinária quantidade de investigações pré-clínicas e clínicas estão explorando o potencial terapêutico das moléculas coestimulatórias positivas e negativas. Aqui, nós revisamos o estado atual do nosso conhecimento dos mecanismos co-estimulatórios da célula T e a inibição dos checkpoints, primariamente do CTLA-4 e do PD-1.

This paper aims to review current treatment of some types of cancer with immunotherapy and immune checkpoint inhibitors. Data sources included original articles, reviews and related texts published over the past 20 years in PubMed, MEDLINE, LILACS and SciELO databases and other online publications. Immune checkpoints normally prevent the body from developing an immune response against healthy cells. Some types of cancer may acquire these checkpoints so that the tumor cells are not recognized by the immune system, preventing it from being activated. Immune checkpoint inhibitors may improve the survival of some patients with advanced malignant tumors, including malignant melanoma, renal cell carcinoma, lymphoma and non-small cell lung cancer. An extraordinary amount of preclinical and clinical investigation is exploring the therapeutic potential of negative and positive costimulatory molecules. Herein, we review the current status of our understanding of T-cell costimulatory mechanisms and checkpoint inhibitors, primarily of CTLA-4 and PD-1.

Immunotherapy and cell therapy for cancer / 中国药理学与毒理学杂志

Cancer immunotherapies are recently gaining attention as viable therapeutic options. There are two types of immunotherapy:passive and active. The passive immunotherapies include several treatments such as monoclonal antibodies,either alone or as antibody-drug conjugates. The active immunotherapies include cancer vaccines which utilize the patient′s own cells as antigen presenting cells and target specific cancer antigens,and chimeric antigen receptor T-cell(CAR-T)therapy which engineers a patient′s T-cells to recognize cancer antigens through chimeric antigen receptors. Recent successes include the US FDA approval of a number of cancer immunotherapies such as treatments utilizing monoclonal antibodies against immune checkpoint inhibitors,the Provenge cancer vaccine that targets prostrate cancer,and a CAR-T against relapsed/refractory acute lymphoblastic leukemia that was designated with breakthrough drug status,all of which has had drug companies investigating cancer immunotherapies with intense enthusiasm. In this review we discuss where the field of immune-oncology stands today,highlight the latest findings and hypothesize future directions.

Synergistic antitumor activity of chemotherapy and immunotherapy in the treatment of established rat solid tumors / 中华微生物学和免疫学杂志

Objective To explore immunotherapy effective combined with active immunotherapy in different time according rats bearing-tumor after paclitaxel and carboplatin chemotherapy, and to identify the optimization time and strategy of vaccine and seek rational chemo-immunotherapy strategies in ovarian cancer treatment. Methods The dynamic immunocytes number and function in established tumor treated with paclitaxel and carboplatin chemotherapy were investigated. The changes of established tumor volume and immune function of different groups were observed according to combining different time after chemotherapy and vaccine. Results Lymphopenia was observed and the number of lymphocyte subset decreased remarkably on the 6th day, but all cells were found almost recovered on 15th day after chemotherapy. There is the process of immune-enhancing from post-chemotherapy 6 day to 10 day and reversal of immune suppression temporary. The combination post-chemotherapy 6 day with CTL caused a significantly delayed tumor growth in both tumor models and induced significant the proliferation of T lymphocyte by [H] 3 releasing. The number of CD8+T cell is the highest, but the expression of Tr cell was lowest in the group of post-chemotherapy 6 day with CTL. Furthermore, the ability of CD8+T secretion IFN-γ is the most in the post-chemotherapy 6 day with immunotherapy groups. Conclusion Combinational paclitaxel and carboplatin chemotherapy has synergistic effects with active immunotherapy boosting against tumor during window periods, where 6 days after chemotherapy with the most decreased number of lymphocytes in the animal periphery might represent the optimal checkpoint for the immune therapy against tumors. Therefore, monitoring the immune status of tumor patients might become one of the important prerequisites for the effective immune therapy when designing the comprehensive therapeutic strategies.

Vaccination with a Recombinant Chicken FGFR-1 Bypasses Immunological Tolerance against Self-FGFR-1 in Mice / 华中科技大学学报（医学）（英德文版）

The possibility that a recombinant protein vaccine based on xenogeneic homologous FGFR-1 of chicken induces production of autoantibodies against self-FGFR-1 in BALB/c mice was examined by using ELISA, Western blot analysis and ELISPOT assay respectively. Autoantibodies against mouse FGFR-1 were identified by Western blot analysis and ELISA. Compared with the two control groups, the number of APBCs, which were detected by ELISPOT assay, was significantly increased in the spleens of mice immunized with cFR1 (P＜0.05). IgG1 and IgG2b, which were detected by ELISA, were the major subclasses and were substantially increased in response to chicken FGFR-1 when compared with control group. The recombinant chicken FGFR-1 protein used as a vaccine can induce autoantibodies against self-FGFR-1 in mice and provide a basis for the active immunotherapy of tumor angiogenesis.

Experimental Study on the Immunoprotective Effect and Mechanism of Action of Specific Active Immunization with Tumor Cell Vaccine / 中国肿瘤生物治疗杂志

Through several murine transplantable tumor models, we studied the immunoprotective effect and mechanism of action of specific active immunization with various tumor cell vaccines (TCV) treated by: (1) Oleum Curcuma Aromatica (OCA, a Chinese anticancer medicament) and its effective monomer ?-elemene; (2) MMC and glutaraldehyde; (3) ~(60)Co and X-ray irradiation; and (4) vaccinia virus (VV) and newcastle disease virus (NDV), including virus infected TCV membrane fraction (Mfr). The reproducible results of immunoprotective effect indicated that the specific active immunotherapy with such TCVs might be of practical value in clinical immunological approaches to cancer therapeutics.