Small extracellular vesicles purification and scale-up.

Exosomes are small extracellular vesicles (sEVs) secreted by cells. With advances in the study of sEVs, they have shown great potential in the diagnosis and treatment of disease. However, sEV therapy usually requires a certain dose and purity of sEVs to achieve the therapeutic effect, but the existing sEV purification technology exists in the form of low yield, low purity, time-consuming, complex operation and many other problems, which greatly limits the application of sEVs.

Development and characterization of a novel neutralizing scFv vectored immunoprophylaxis against botulinum toxin type A.

Botulinum toxin is a protein toxin secreted by Clostridium botulinum that is strongly neurotoxic. Due to its characteristics of being super toxic, quick acting, and difficult to prevent, the currently reported antiviral studies focusing on monoclonal antibodies have limited effectiveness. Therefore, for the sake of effectively prevention and treatment of botulism and to maintain country biosecurity as well as the health of the population, in this study, we intend to establish a single chain antibody (scFv) targeting the carboxyl terminal binding functional domain of the botulinum neurotoxin heavy chain (BONT/AHc) of botulinum neurotoxin type A, and explore the value of a new passive immune method in antiviral research which based on adeno-associated virus (AAV) mediated vector immunoprophylaxis (VIP) strategy.

Bispecific antibodies targeting EGFR/Notch enhance the response to talazoparib by decreasing tumour-initiating cell frequency.

Poly ADP ribose polymerase (PARP) inhibitors are mainly used in treating BRCA-mutant cancers, and their application in novel therapies to expand their benefit is of interest in personalized medicine. A recent report showed that pharmacological targeting of PARP increases the sensitivity of cancer cells to EGFR inhibition, but the therapeutic value of this combination has not been fully determined. We propose a strategy of combining PARP inhibitors with bispecific antibodies that target both EGFR and Notch signalling, highlighting the difficulties posed by deregulation of Notch signalling and the enrichment of cancer stem cells (CSCs) during therapy.

Engineered soluble ACE2 receptor: Responding to change with change.

SARS coronavirus 2 (SARS-CoV-2) invades the human body by binding to major receptors such as ACE2 its S-spike protein, so the interaction of receptor-binding sites has been a hot topic in the development of coronavirus drugs. At present, the clinical progress in monoclonal antibody therapy that occurred early in the pandemic is gradually showing signs of slowing. While recombinant soluble ACE2, as an alternative therapy, has been modified by many engineering methods, both the safety and functional aspects are approaching maturity, and this therapy shows great potential for broadly neutralizing coronaviruses, but its progress in clinical development remains stalled.

The roles of small extracellular vesicles in cancer and immune regulation and translational potential in cancer therapy.

Extracellular vesicles (EVs) facilitate the extracellular transfer of proteins, lipids, and nucleic acids and mediate intercellular communication among multiple cells in the tumour environment. Small extracellular vesicles (sEVs) are defined as EVs range in diameter from approximately 50 to 150 nm. Tumour-derived sEVs (TDsEVs) and immune cell-derived sEVs have significant immunological activities and participate in cancer progression and immune responses.

Therapeutic antibodies under development for SARS-CoV-2.

The world is experiencing one of the most difficult moments in history with COVID-19, which has rapidly developed into a worldwide pandemic with a significant health and economic burden. Efforts to fight the virus, including prevention and treatment, have never stopped. However, no specific drugs or treatments have yet been found.

CAR Macrophages for SARS-CoV-2 Immunotherapy.

Targeted therapeutics for the treatment of coronavirus disease 2019 (COVID-19), especially severe cases, are currently lacking. As macrophages have unique effector functions as a first-line defense against invading pathogens, we genetically armed human macrophages with chimeric antigen receptors (CARs) to reprogram their phagocytic activity against SARS-CoV-2. After investigation of CAR constructs with different intracellular receptor domains, we found that although cytosolic domains from MERTK (CAR) did not trigger antigen-specific cellular phagocytosis or killing effects, unlike those from MEGF10, FcRγ and CD3ζ did, these CARs all mediated similar SARS-CoV-2 clearance .

Ig-like ACE2 protein therapeutics: A revival in development during the COVID-19 pandemic.

While the potential therapeutic utility of angiotensin-converting enzyme 2 (ACE2) is well established, the clinical development of ACE2 drugs has been limited, likely due in part to the short half-life of the protein. In contrast, Ig-like ACE2 fusion proteins have exhibited greatly extended plasma half-life in vivo, and they have been shown to have a potent neutralization effect against SARS-CoV-2. Clinical investigation of Ig-like ACE2 fusion proteins as COVID-19 interventions is thus warranted.

Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, at the end of 2019, and there are currently no specific antiviral treatments or vaccines available. SARS-CoV-2 has been shown to use the same cell entry receptor as SARS-CoV, angiotensin-converting enzyme 2 (ACE2). In this report, we generate a recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1.

CAR exosomes derived from effector CAR-T cells have potent antitumour effects and low toxicity.

Genetically engineered T cells expressing a chimeric antigen receptor (CAR) are rapidly emerging a promising new treatment for haematological and non-haematological malignancies. CAR-T therapy can induce rapid and durable clinical responses but is associated with unique acute toxicities. Moreover, CAR-T cells are vulnerable to immunosuppressive mechanisms.