IMT504 is a novel immunomodulatory
oligonucleotide that has shown immunotherapeutic properties in early preclinical and clinical studies.
IMT504 was tested in a neutropenic rat model of Pseudomonas aeruginosa
bacteremia and
sepsis. This animal system recapitulates many of the
pathological processes found in neutropenic patients with
Gram-negative, bacterial infections. The research was conducted in the setting of an academic research laboratory. The test subjects were Sprague-Dawley rats. Animals were rendered neutropenic by administration of
cyclophosphamide, colonized with P. aeruginosa by oral feeding, and then randomized to receive
IMT504 over a range of doses and treatment regimens representing early and late therapeutic interventions.
IMT504 immunotherapy conferred a significant survival advantage over the 12-day study period compared with the results seen with placebo-treated animals when the
therapy was administered at the onset of
neutropenia and even in the absence of
antibiotics and after the onset of
fever and systemic
infection. Notably, even late salvage
IMT504 monotherapy was highly effective (13/14 surviving rats with
IMT504 therapy versus 2/14 controls, P=<0.001). Moreover, late salvage
IMT504 monotherapy was as effective as
antibiotic therapy (13/14 surviving rats versus 21/21 rats, P=0.88). In addition, no antagonism or loss of therapeutic efficacy was noted with combination
therapy of
IMT504 plus
antibiotics.
IMT504 immunotherapy provides a remarkable survival advantage in
bacteremia and
sepsis in neutropenic animals and deserves further study as a new treatment option in patients with, or at risk for, severe
Gram-negative bacterial infections and
sepsis.