Research progress in optimization of therapeutic effect of antibodies against flavivirus / 中华微生物学和免疫学杂志

Flaviviruses are a class of positive-strand RNA viruses mainly transmitted by arthropods, which can cause high mortality and morbidity worldwide. At present, there is no specific therapy. Therapeutic antibodies bring hope for the treatment of flavivirus infection, but the antibody-dependent enhancement (ADE) effect induced by flavivirus infection can lead to disease progression. The ideal therapeutic antibodies against flaviviruses should not only treat flavivirus infection, but also avoid the harm caused by ADE. Therefore, researchers have optimized some of the antibodies to seek the best therapeutic antibodies. This review briefly described the research progress and mechanism of therapeutic antibodies against flaviviruses as well as some strategies to reduce the ADE effect induced by the therapeutic antibodies.

Differential discovery strategies of therapeutic antibody drugs / 生物工程学报

Therapeutic antibody drugs have achieved great success in clinical practice. However, their efficacy and safety still need to be improved. At the same time, excessive concentration of drug targets will cause problems such as repeated development and waste of resources. Therefore, pharmaceutical companies need to explore differentiated discovery strategies when researching antibody drugs in order to survive and develop in the fierce market competition. In this paper, the differential development strategy of therapeutic antibody drugs is discussed from the aspects of drug sources and formats, drug target selection, drug mechanism and differential drug characteristics.

Effect of extracellular cyclophilin A on inflammatory response and anti-inflammatory activity of antibody against cyclophilin A / 生物工程学报

Cyclophilin A (CypA) is a member of peptidyl prolylisomerases (PPIase) family. CypA is best known as a ubiquitously distributed intracellular protein. It has also been shown to be secreted by cells in response to inflammatory stimuli and oxidative stress. Extracellular CypA (eCypA) interacts with CD147 to initiate inflammatory responses via recruiting leucocytes into inflamed tissue. Recombinant CypA was expressed in Escherichia coli and then purified using Superdex 75™ 16/60. The results of Real-time PCR and ELISA showed that the expression levels of proinflammatory cytokines, such as IL-1β, secreted by eCypA stimulated BMDM were significantly up-regulated, indicating that eCypA played an important role in promoting inflammatory responses. In addition, anti-CypA antibody was prepared using purified CypA protein for therapeutic evaluation in a mouse model of LPS-induced acute lung inflammation. Antibody-treated mice showed reduced lung injury and the expression levels of IL-1β in the lung tissue and blood were decreased significantly, indicating that anti-CypA antibody exerted a potent anti-inflammatory activity. Our findings provide a potential therapeutic antibody for inflammation-mediated diseases.

Crystal clear: visualizing the intervention mechanism of the PD-1/PD-L1 interaction by two cancer therapeutic monoclonal antibodies

Antibody-based PD-1/PD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre-existing T-cell function to modulate antitumor immunity. In this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-1/PD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural information will benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.

Anti-Ebola virus therapeutic antibody: Research advances / 国际药学研究杂志

Ebola virus (EBOV) is a virulent virus, which can cause the occurrence of EBOV hemorrhagic fever with the mortality of 50%-90% in human and non-human primate (NHP) animal. The biohazard level of Ebola is BSL-4, which is higher than that of AIDS and SARS (BSL-3). Since 2014, the EBOV has spread in West Africa and taken away thousands of lives. At present, the prevention or therapeutic drugs in research against EBOV include vaccines, small molecule drugs and antibodies. Antibodies are relatively safe and specific with fewer side effects. There have reports of several functional antibodies, including monoclonal antibodies 16F6, KZ52 and "antibody cocktails" such as MB-003, ZMAb and ZMapp, which have better efficacy than monovalent antibodies; in China, a similar antibody combination, MIL77, has also completed the preclinical studies for emergency use. In this paper, the development of the antiEbola therapeutic antibodies is reviewed.