Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently become a pandemic. As the sudden emergence and rapid spread of SARS-CoV-2 is endangering global health and the economy, the development of strategies to contain the virus's spread are urgently needed. At present, various diagnostic kits to test for SARS-CoV-2 are available for use to initiate appropriate treatment faster and to limit further spread of the virus. Several drugs have demonstrated in vitro activity against SARS-CoV-2 or potential clinical benefits. In addition, institutions and companies worldwide are working tirelessly to develop treatments and vaccines against COVID-19. However, no drug or vaccine has yet been specifically approved for COVID-19. Given the urgency of the outbreak, we focus here on recent advances in the diagnostics, treatment, and vaccine development for SARS-CoV-2 infection, helping to guide strategies to address the current COVID-19 pandemic.
1 January 2020 in Clinical & Translational Immunology
Objectives: Triple‐negative breast cancer (TNBC) is well known for its strong invasiveness, rapid recurrence and poor prognosis. Immunotherapy, including chimeric antigen receptor‐modified T (CAR‐T) cells, has emerged as a promising tool to treat TNBC. The identification of a specific target tumor antigen and the design of an effective CAR are among the many challenges of CAR‐T therapy.Methods: We reported that epidermal growth factor receptor (EGFR) is highly expressed in TNBC and consequently designed an optimal third generation of CAR targeting EGFR. The efficacy of primary T lymphocytes infected with EGFR CAR lentivirus (EGFR CAR‐T) against TNBC was evaluated both in vitro and in vivo. The signalling pathways activated in tumor and EGFR CAR‐T cells were revealed by RNA sequencing analysis.Results: Third‐generation EGFR CAR‐T cells exerted potent and specific suppression of TNBC cell growth in vitro, whereas limited cytotoxicity was observed towards normal breast epithelial cells or oestrogen receptor‐positive breast cancer cells. This capability was further demonstrated in vivo in a xenograft mouse model, with minimal off‐tumor cytotoxicity. Mechanistically, in vitro stimulation with TNBC cells induced the expansion of naïve‐associated EGFR CAR‐T cells and enhanced their persistence. Furthermore, EGFR CAR‐T cells activated the interferon γ, granzyme–perforin–PARP and Fas–FADD–caspase signalling pathways in TNBC cells.Conclusion: We demonstrate that EGFR is a relevant immunotherapeutic target in TNBC, and EGFR CAR‐T exhibits potent and specific antitumor activity against TNBC, suggesting the potential of this third‐generation EGFR CAR‐T as an immunotherapy tool to treat TNBC in the clinic.
Infectious diseases, caused by pathogenic microorganisms, are capable of affecting crises. In addition to persistent infectious diseases such as malaria and dengue fever, the vicious outbreaks of infectious diseases such as Neocon, Ebola and SARS-CoV-2 in recent years have prompted the search for more efficient and convenient means for better diagnosis and treatment. Antibodies have attracted a lot of attention due to their good structural characteristics and applications. Nanobodies are the smallest functional single-domain antibodies known to be able to bind stably to antigens, with the advantages of high stability, high hydrophilicity, and easy expression and modification. They can directly target antigen epitopes or be constructed as multivalent nanobodies or nanobody fusion proteins to exert therapeutic effects. This paper focuses on the construction methods and potential functions of nanobodies, outlines the progress of their research, and highlights their various applications in human infectious diseases.
T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens, thereby engaging with CD3 on the T cell receptor. This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells. These antibodies have emerged as one of the most promising avenues within tumor immunotherapy. However, despite success in treating hematological malignancies, significant advancements in solid tumors have yet to be explored. In this review, we aim to address the critical challenges associated with T cell-redirecting bispecific antibodies and explore novel strategies to overcome these obstacles, with the ultimate goal of expanding the application of this therapy to include solid tumors.
Respiratory syncytial virus (RSV) poses a significant public health challenge, especially among children. Although palivizumab and nirsevimab, neutralizing antibodies (nAbs) targeting the RSV F protein, have been used for prophylaxis, their limitations underscore the need for more effective alternatives. Herein, we present a potent and broad nAb, named 5B11, which exhibits nanogram level of unbiased neutralizing activities against both RSV-A and -B subgroups. Notably, 5B11 shows a ~20-fold increase in neutralizing efficacy compared to 1129 (the murine precursor of palivizumab) and approximately a 3-fold increase in neutralizing efficacy against B18537 in comparison to nirsevimab. Cryo-electron microscopy analysis reveals 5B11’s mechanism of action by targeting a highly conserved epitope within site V, offering a promising strategy with potentially lower risk of escape mutants. Antiviral testing in a female cotton rat model demonstrated that low-dose (1.5 mg/kg) administration of 5B11 achieved comparable prophylactic efficacy to that achieved by high-dose (15 mg/kg) of 1129. Furthermore, the humanized 5B11 showed a superior in vivo antiviral activity against B18537 infection compared to nirsevimab and palivizumab. Therefore, 5B11 is a promising RSV prophylactic candidate applicable to broad prevention of RSV infection.