Preclinical evaluation of VAX-IP, a novel bacterial minicell-based biopharmaceutical for nonmuscle invasive bladder cancer.
The development of new therapies that can prevent recurrence and progression of nonmuscle invasive bladder cancer remains an unmet clinical need. The continued cost of monitoring and treatment of recurrent disease, along with its high prevalence and incidence rate, is a strain on healthcare economics worldwide. The current work describes the characterization and pharmacological evaluation of VAX-IP as a novel bacterial minicell-based biopharmaceutical agent undergoing development for the treatment of nonmuscle invasive bladder cancer and other oncology indications. VAX-IP minicells selectively target two oncology-associated integrin heterodimer subtypes to deliver a unique bacterial cytolysin protein toxin, perfringolysin O, specifically to cancer cells, rapidly killing integrin-expressing murine and human urothelial cell carcinoma cells with a unique tumorlytic mechanism. The in vivo pharmacological evaluation of VAX-IP minicells as a single agent administered intravesically in two clinically relevant variations of a syngeneic orthotopic model of superficial bladder cancer results in a significant survival advantage with 28.6% (P = 0.001) and 16.7% (P = 0.003) of animals surviving after early or late treatment initiation, respectively. The results of these preclinical studies warrant further nonclinical and eventual clinical investigation in underserved nonmuscle invasive bladder cancer patient populations where complete cures are achievable.
Vaxiion Therapeutics , San Diego, California, USA.
Shingo
S
Tsuji
Department of Chemical & Biomolecular Engineering, Tulane University , New Orleans, Louisiana, USA.
Xuguang
X
Chen
Vaxiion Therapeutics , San Diego, California, USA.
Bryan
B
Hancock
Vaxiion Therapeutics , San Diego, California, USA.
Veronica
V
Hernandez
Vaxiion Therapeutics , San Diego, California, USA.
Barbara
B
Visentin
Vaxiion Therapeutics , San Diego, California, USA.
Katherine
K
Reil
Vaxiion Therapeutics , San Diego, California, USA.
Roger
R
Sabbadini
Vaxiion Therapeutics , San Diego, California, USA.
Matthew
M
Giacalone
Department of Chemical & Biomolecular Engineering, Tulane University , New Orleans, Louisiana, USA.
W T
WT
Godbey