Characterization of Pseudomonas aeruginosa ghost and evaluation of its immune proficiency in Nile tilapia (Oreochromis niloticus)
Authors: Ghazy, Haneen A.; El-Nahas, Abeer F.; Mahmoud, Shawky A.; Fahmy, Hanan A.; El-Domany, Ramadan A.; Mahmoud, Hoda E.; Omar, Amira A.
Pseudomonas aeruginosais known to be multidrug-resistant organisms so its infection is challenging. This study aimed to use the sponge-like reduced protocol in preparation ofP. aeruginosaghosts (PAGs) as a vaccine alternative and evaluate its competency in stimulating the immune response in Nile tilapia. Characterization of PAGs was done using the light, fluorescent and transmission electron microscope. 240 fish have been divided into four groups (60 fish each; three groups were injected with a high, medium, or low dose of PAGs, and a control group. Total and differential leukocyte count, phagocytic activity, lysozyme activity, and gene expression of some immune-related genes were done after the first and booster ghost dose injection. All fish groups were challenged intraperitoneally withP. aeruginosa(1 x 10(7) CFU ml(-1)); the mean percent mortality was calculated. Significant immunization potency of the large dose of PAGs was prominent. It is associated with a significant increased number of WBCs, heterophile, lymphocytes, and monocytes. Also the phagocytic activity and indexes were significantly increased by the high and moderate dose of PAGs. Additionally, significant upregulation of immune-related gene (MHC-II)and inflammatory-related gene (IL8) and maintained expression level ofTLR7were recorded.We conclude that chemically preparedP. aeruginosaghosts maintained both the 3D structure and surface molecules of live bacteria and also are capable of inducing specific immune responses in Nile Tilapia, and reduced mortalities in challenged fish.Our results indicate the advantage of this procedure for production of bacterial ghost, which can be used in wide a range of hosts.
Phase I trial of HuMax-IL8 (BMS-986253), an anti-IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors
JOURNAL FOR IMMUNOTHERAPY OF CANCER
Authors: Bilusic, Marijo; Heery, Christopher R.; Collins, Julie M.; Donahue, Renee N.; Palena, Claudia; Madan, Ravi A.; Karzai, Fatima; Marte, Jennifer L.; Strauss, Julius; Gatti-Mays, Margaret E.; Schlom, Jeffrey; Gulley, James L.
Background HuMax-IL8 (now known as BMS-986253) is a novel, fully human monoclonal antibody that inhibits interleukin-8 (IL-8), a chemokine that promotes tumor progression, immune escape, epithelial-mesenchymal transition, and recruitment of myeloid-derived suppressor cells. Studies have demonstrated that high serum IL-8 levels correlate with poor prognosis in many malignant tumors. Preclinical studies have shown that IL-8 blockade may reduce mesenchymal features in tumor cells, making them less resistant to treatment. Methods Fifteen patients with metastatic or unresectable locally advanced solid tumors were enrolled in this 3 + 3 dose-escalation trial at four dose levels (4, 8, 16, or 32 mg/kg). HuMax-IL8 was given IV every 2 weeks, and patients were followed for safety and immune monitoring at defined intervals up to 52 weeks. Results All enrolled patients (five chordoma, four colorectal, two prostate, and one each of ovarian, papillary thyroid, chondrosarcoma, and esophageal) received at least one dose of HuMax-IL8. Eight patients had received three or more prior lines of therapy and five patients had received prior immunotherapy. Treatment-related adverse events occurred in five patients (33%), mostly grade 1. Two patients receiving the 32 mg/kg dose had grade 2 fatigue, hypophosphatemia, and hypersomnia. No dose-limiting toxicities were observed, and maximum tolerated dose was not reached. Although no objective tumor responses were observed, 11 patients (73%) had stable disease with median treatment duration of 24 weeks (range, 4-54 weeks). Serum IL-8 was significantly reduced on day 3 of HuMax-IL8 treatment compared to baseline (p = 0.0004), with reductions in IL-8 seen at all dose levels. Conclusions HuMax-IL8 is safe and well-tolerated. Ongoing studies are evaluating the combination of IL-8 blockade and other immunotherapies.