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81.
The extraordinary advantages associated with mRNA vaccines,including their high efficiency,relatively low severity of side effects,and ease of manufacture,have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers.Nevertheless,most mRNA delivery carriers have many disadvantages,such as high toxicity,poor biocompatibility,and low efficiency in vivo,which have hindered the widespread use of mRNA vaccines.To further characterize and solve these proble...  相似文献   
82.
Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRPα triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRPα resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses. Four different antibody molecules designed to target the CD47-SIRPα interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148. Hu5F9-G4, a humanized anti-CD47 blocking antibody is currently being studied in four different Phase I trials. These studies may lay the groundwork for therapeutic bispecific antibodies. Bispecific antibody (CD20-CD47SL) fusion of anti-CD20 (Rituximab) and anti-CD47 also demonstrated a synergistic effect against lymphoma in preclinical models. This review summarizes the large body of preclinical evidence and emerging clinical data supporting the use of antibodies designed to target the CD47-SIRPα interaction in leukemia, lymphoma and multiple myeloma.  相似文献   
83.
Acute lymphoblastic leukemia (ALL) is one of the most common cancer diagnoses identified in adolescents and young adults (AYAs). Although most children with ALL are cured of their disease, AYAs have experienced much worse outcomes over time, with event-free survival ranging from 30 to 45%. This survival disparity is likely due to differences in tumor biology, treatment-related toxicities, and nonmedical issues. This review summarizes these differences as well as focusing on the various trials that have demonstrated superior outcomes with pediatric protocols in AYAs with ALL. Even with the widespread use of these protocols, a treatment gap remains, and novel therapies are one way to address this problem. Still, these therapies also have significant toxicities and unique issues that need to be tested further, especially in the AYA population. The development of more AYA-specific trials will be an important way to examine novel therapies and interventions designed to reduce treatment-related toxicities and improve long-term outcomes.  相似文献   
84.
Monoclonal antibody-based targeted therapy has greatly improved treatment options for patients. However, long-term efficacy of such antibodies is limited by resistance mechanisms. New insights into the mechanisms by which tumors evade immune control have driven innovative therapeutic strategies to eliminate cancer by re-directing immune cells to tumors. Advances in protein engineering technology have generated multiple bispecific antibody (BsAb) formats capable of targeting multiple antigens as a single agent. Approval of two BsAb and three check point blocking mAbs represent a paradigm shift in the use of antibody constructs. Since BsAbs can directly target immune cells to tumors, drug resistance and severe adverse effects are much reduced. The wave of next generation “bispecific or multispecific antibodies” has advanced multiple candidates into ongoing clinical trials. In this review, we focus on preclinical and clinical studies in hematological malignancies as well as discuss reasons for the limited success of BsAbs against solid tumors.  相似文献   
85.
胆管癌发病率低,恶性程度高,预后差。吉西他滨联合顺铂是晚期胆管癌的标准一线治疗,其疗效并不突出;同时,胆管癌缺乏标准二线治疗,亟需探索新的治疗方法。抗表皮生长因子受体、血管内皮生长因子、人类表皮生长因子受体-2等分子靶向治疗在化疗基础上均无突破,但靶向成纤维细胞生长因子受体2基因融合、IDH1/2基因突变等新靶点的治疗展现出前景。免疫检查点抑制剂、细胞因子、过继细胞治疗、肿瘤疫苗等免疫治疗也正在胆管癌中进行尝试。本文将对晚期胆管癌的药物治疗现状进行综述。  相似文献   
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Chimeric antigen receptors (CAR)-T cell therapy has recently made promising advances towards treatment of B-cell malignancies. This approach makes use of an antibody-derived single chain variable fragment (scFv)-based CAR to target the CD19 antigen. Currently scFvs are the most common strategy for creation of CARs, but tumor cells can also be targeted using non-antibody based approaches with designs focused on the interaction between natural receptors and their ligands. This emerging strategy has been used in unique ways to target multiple tumor types, including solid and haematological malignancies. In this review, we will highlight the performance of receptor-ligand combinations as designs for CARs to treat cancer, with a particular focus on haematologic malignancies.  相似文献   
89.
《Annales d'endocrinologie》2018,79(5):591-595
The present final consensus statement of the French Society of Endocrinology lays out the assessments that are to be systematically performed before and during anticancer treatment by immunotherapy, tyrosine kinase inhibitors or mTOR inhibitors, even without onset of any endocrinopathy. It also discusses the CTCAE adverse event grading system in oncology and the difficulty of implementing it for endocrine side-effects of these anticancer treatments. Notably, this is why certain treatment steps applied in other side-effects (e.g., high-dose corticosteroids, contraindications to immunotherapy, etc.) need to be discussed before implementation for endocrine side-effects.  相似文献   
90.
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