Selinexor Combined with Ibrutinib Demonstrates Tolerability and Safety in Advanced B-Cell Malignancies: A Phase I Study.

Purpose: Dual blockade of Bruton's tyrosine kinase with ibrutinib and selinexor has potential to deepen responses for patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL).

Patients And Methods: In this phase I study (clinicaltrials.gov: NCT02303392), adult patients with CLL/NHL, relapsed/refractory to ≥1 prior therapy were enrolled.

Characterization of a Cynomolgus Macaque Model of Pneumonic Plague for Evaluation of Vaccine Efficacy.

The efficacy of a recombinant plague vaccine (rF1V) was evaluated in cynomolgus macaques (CMs) to establish the relationship among vaccine doses, antibody titers, and survival following an aerosol challenge with a lethal dose of Yersinia pestis strain Colorado 92. CMs were vaccinated with a range of rF1V doses on a three-dose schedule (days 0, 56, and 121) to provide a range of survival outcomes. The humoral immune response following vaccination was evaluated with anti-rF1, anti-rV, and anti-rF1V bridge enzyme-linked immunosorbent assays (ELISAs).

Cynomolgus macaque model for pneumonic plague.

A recombinant vaccine (rF1V) is currently being developed for protection against pneumonic plague. An essential component in evaluating efficacy of the rF1V vaccine is the development of a well-understood animal model that shows similarity to human disease. The objective of this study was to determine the inhaled median lethal dose (LD₅₀), evaluate the pathophysiology of disease and identify appropriate study endpoints in a cynomolgus macaque (CM) model of pneumonic plague.

A human antibody against anthrax protective antigen protects rabbits from lethal infection with aerosolized spores.

ALXN4100, a fully human antibody that binds to the protective antigen of anthrax toxin, was generated from a Fab isolated from a phage display library and was analyzed for its pharmacokinetic properties in rabbits and then used to protect rabbits from challenge with a lethal aerosol dose of Bacillus anthracis spores (approximately 322X LD(50)). All rabbits receiving 15 or 40 mg/kg of antibody 24 hours before challenge survived; survival of rabbits receiving 4 mg/kg either subcutaneously or intravenously was 80 or 90%, respectively. Susceptibility to anthrax disease appeared to be correlated with serum antibody concentration.

Yersinia pseudotuberculosis produces a cytotoxic necrotizing factor.

Cell extracts from Yersinia pseudotuberculosis induced multinucleation in HEp-2 cells in a manner similar to the effect caused by Escherichia coli cytotoxic necrotizing factor (CNF). The activity was not dependent on the Yersinia 70-kb virulence plasmid, and the activity was not inhibited by antibodies capable of neutralizing E. coli CNF type 1.