AR vaccine(Madison Vaccines, Inc.)

Preclinical studies demonstrated that a DNA vaccine (pTVG-AR, MVI-118) encoding the androgen receptor ligand-binding domain (AR LBD) augmented antigen-specific CD8+ T cells, delayed prostate cancer progression and emergence of castration-resistant disease, and prolonged survival of tumor-bearing mice. This vaccine was evaluated in a multicenter phase I trial.

Patients with metastatic castration-sensitive prostate cancer (mCSPC) who had recently begun androgen deprivation therapy were randomly assigned to receive pTVG-AR on one of two treatment schedules over one year, and with or without GM-CSF as a vaccine adjuvant. Patients were followed for 18 months. Primary objectives were safety and immune response. Secondary objectives included median time to PSA progression, and 18-month PSA-PFS (PPFS).

Forty patients were enrolled at three centers. Twenty-seven patients completed treatment and 18 months of follow-up. Eleven patients (28%) had a PSA progression event before the 18-month time point. No grade 3 or 4 adverse events were observed. Of 30 patients with samples available for immune analysis, 14 (47%) developed Th1-type immunity to the AR LBD, as determined by IFNγ and/or granzyme B ELISPOT. Persistent IFNγ immune responses were observed irrespective of GM-CSF adjuvant. Patients who developed T-cell immunity had a significantly prolonged PPFS compared with patients without immunity (HR = 0.01; 95% CI, 0.0–0.21; P = 0.003).

pTVG-AR was safe and immunologically active in patients with mCSPC. Association between immunity and PPFS suggests that treatment may delay the time to castration resistance, consistent with preclinical findings, and will be prospectively evaluated in future trials.See related commentary by Shenderov and Antonarakis, p. 5056

Objective:To observe the therapeutic effect of local combination（LC） of myrtle oil, anthocyanin and hyaluronic acid on allergic rhinitis in rats exposed to PM2.5 and explore its mechanism. Method:The rats were randomly divided into 5 groups: normal group, LC group, AR group, AR+PM2.5group and AR+PM2.5+LC. After successful establishment of the model, AR+PM2.5 group and AR+PM2.5+ LC group were intranasally dripped with PM2.5 suspension, while LC group and AR+PM2.5+ LC group were intranasally dripped with LC. The AR symptom score was observed. The eosinophil infiltration in nasal mucosa was observed by hematoxylin-eosin staining. The ultrastructural changes were observed by transmission electron microscope, the level of immunoglobulin IgE, IL-6, IL-8 and TNF-α in serum was detected by enzyme-linked immunosorbent assay, the expression of NF-κBp65 and phosphorylated p38MAPK in nasal mucosa was detected by immunohistochemical staining. Result:There were no significant differences in symptoms, eosinophil infiltration and tissue ultrastructure between normal group and LC group（P>0.05）, but the symptom score, nasal mucosal eosinophil infiltration and serum IgE level in AR group and AR+PM2.5 group were significantly higher than those in normal group（P<0.05）, especially in AR+PM2.5 group（P<0.05）. Compared with AR group and AR+PM2.5 group, the symptom score, eosinophil infiltration and IgE level in AR+PM2.5+LC group were significantly decreased（P<0.05）, and the ultrastructural damage was also significantly improved. Compared with normal group, NF-κBp65, phosphorylated p38MAPK and serum inflammatory factors in AR group and AR+PM2.5 group were increased（P<0.05）, and those in AR+PM2.5 group were higher than those in AR group（P<0.05）. Compared with AR group and AR+PM2.5 group, the expression of inflammatory factors and NF-κBp65 and phosphorylated p38MAPK in nasal mucosa in AR+PM2.5+LC group decreased significantly（P<0.05）. Conclusion:LC has good safety in the treatment of nasal drip and has a significant therapeutic effect on allergic rhinitis rats exposed to PM2.5, which may alleviate the effect of PM2.5 on allergic rhinitis rats by regulating excessive activation of NF-κB and MAPK pathway and reducing eosinophil infiltration and IgE production.