Superantigen-fused T cell engagers for tumor antigen-mediated robust T cell activation and tumor cell killing.

Inadequate T cell activation has severely limited the success of T cell engager (TCE) therapy, especially in solid tumors. Enhancing T cell activity while maintaining the tumor specificity of TCEs is the key to improving their clinical efficacy. However, currently, there needs to be more effective strategies in clinical practice. Here, we design novel superantigen-fused TCEs that display robust tumor antigen-mediated T cell activation effects. These innovative drugs are not only armed with the powerful T cell activation ability of superantigens but also retain the dependence of TCEs on tumor antigens, realizing the ingenious combination of the advantages of two existing drugs. Superantigen-fused TCEs have been preliminarily proven to have good (>30-fold more potent) and specific (>25-fold more potent) antitumor activity in vitro and in vivo. Surprisingly, they can also induce the activation of T cell chemotaxis signals, which may promote T cell infiltration and further provide an additional guarantee for improving TCE efficacy in solid tumors. Overall, this proof-of-concept provides a potential strategy for improving the clinical efficacy of TCEs.

Hormones other than aldosterone may contribute to hypertension in 3 different subtypes of primary aldosteronism.

Blood pressure (BP) level is similar in patients with 3 subtypes of primary aldosteronism (PA), even though aldosterone levels may vary. Glucocorticoids and adrenomedullary hormones may be influenced and may contribute to hypertension in PA. The authors' objective was to investigate the influence of PA on adrenal gland secretion and the roles of these hormones in hypertension. Patients diagnosed with PA (229 cases) were enrolled and classified into 3 subgroups: aldosterone-producing adenoma (APA), unilateral nodular adrenal hyperplasia (UNAH), and idiopathic hyperaldosteronism (IHA). Patients with essential hypertension served as the control group (100 cases). Concentration of the above hormones was measured and compared between groups. Level of plasma adrenocorticotrophic hormone (ACTH) in patients with APA was significantly lower than that in patients with IHA (P<.001) and UNAH (P<0.5). The 24-hour urinary free cortisol and adrenomedullary hormone levels were highest in patients with IHA, lower in patients with APA, and lowest in patients with UNAH. Systolic BP level was positively correlated with 8 am plasma cortisol level (r=0.142, P=.039) and plasma ACTH level (r=0.383, P=.016). Cortisol and adrenomedullary hormones were different between PA subtypes and they might involve regulation of BP in those patients.

[Clinical characteristics and surgery outcomes of unilateral nodular adrenal hyperplasia in primary aldosteronism: study of 145 cases].

OBJECTIVE: To investigate the clinical characteristics, differential diagnosis, and surgery outcome of unilateral nodular adrenal hyperplasia (UNAH). METHODS: The clinical data of 145 patients with primary aldosteronism, 67 males and 78 females, aged 37.9 (19-60), including 78 cases of aldosterone-producing adenoma (APA), 14 cases of UNAH, and 55 cases of idiopathic bilateral adrenal hyperplasia (BAH), were collected. Radioimmunoassay was used to examine the blood and urine aldosterone and plasma rennin activity. Automatic biochemical apparatus was used to examine the blood and urine electrolytes, renal functions, and urine microalbumin. Twelve-lead electrocardiography, echocardiography, and plain scanning of enhanced CT scanning of the bilateral adrenals were conducted. Adrenal venous sampling (AVS) was conducted in 62 patients to collect blood samples from vena cava and bilateral suprarenal veins to detect the levels of aldosterone and cortisol. All UNAH patients and 3 BAH patients underwent unilateral adrenalectomy and three APA patients underwent unilateral adrenalectomy or adenoma resection. Then the patients were followed up for 39.2 months. RESULTS: The incidence of UNAH is 9.7% in the primary aldosteronism patients. There were no significant differences in age, gender, duration of hypertension, blood pressure (SBP, DBP), and indexes indicating damages in target organs of hypertension (left ventricular hypertrophy rate, blood creatinine, urine microalbumin, etc) among these three groups. The level of serum potassium of the APA group was significantly lower than that of the BAH group (P < 0.01), and the levels of plasma and urine aldosterone of the APA group were significantly higher than those of the BAH group (P < 0.05 and P < 0.01). The serum potassium of the UNAH group was higher than that of the APA group and lower than that of the BAH group, and the levels of plasma and urine aldosterone of the UNAH group were both higher than those of the APA group and lower than those of the BAH group, however all not significantly (all P > 0.05). The coincidence rate of CT was 50% (7/14) in the UNAH group. The accuracy of AVS for diagnosis of UNAH was 85.7% (12/14). After operation, the serum potassium and plasma aldosterone concentrations returned normal in all the UNAH patients. Blood pressure returned to normal in 50% (7/14) of the UNAH patients, and was improved in the other 50% (7/14) patients. CONCLUSION: UNAH can be cured by adrenal surgery. The diagnostic values of clinical examination and adrenal CT are limited. AVS is essential in diagnosing UNAH patients.