BGB-A445, a novel non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical models / 医学前沿

OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.

Sleep quality and its influencing factors in senior high school students / 中国学校卫生

Objective@#To study the current situation of sleep quality of senior high school students and analyze the influencing factors, so as to provide a reference for targeted sleep quality improvement of high school students.@*Methods@#A total of 4 793 senior high school students of different grades were recruited from four different regions (Shanghai, Qinghai, Macao, Henan) in 2020. The information of demographic, sleep status, mental factors, living habits and other information were collected by questionnaire. Descriptive statistics and Logistic regression were used to analyze sleep quality and its influencing factors of the senior high school students.@*Results@#About 24.2% of senior high school students reported sleep problems and 71.4% slept less than 7 hours at night. Interpersonal sensitivity, depression, anxiety symptoms, learning, family and interpersonal stress had significant effects on sleep problems in senior high school students( χ 2=1 147.98, 1 228.35, 1 032.54, 371.05, 497.61, 475.39, P <0.01). Drinking coffee and tea, drinking alcohol, smoking (including secondhand smoke), long term use of electronic products, late sleep, bedtime diet, poor sleep environment, parents with sleep problems were the risk factors for sleep disorders of senior high school students, regular exercise was the protective factors for sleep disorders of senior high school students, the influence was significant ( χ 2=160.28, 127.73 , 108.02, 113.27, 470.91, 340.95, 72.02, 155.53, 116.30, 76.96, 28.75, 12.89, P <0.05).@*Conclusion@#The sleep quality of senior high school students needs to be improved. Schools and parents should pay attention to the mental health and living habits of senior high school students to help them improve their sleep quality and grow up smoothly.