Effect of Allocetra-OTS (off-the-shelf apoptotic cells) Therapy in Sepsis

Abstract

Background & Aim Sepsis, which has been identified by the World Health Organization (WHO) as a global health priority, has no proven pharmacologic treatment other than appropriate antibiotic agents, fluids, vasopressors as needed, and possibly corticosteroids. Reported death rates among hospitalized patients are up to 45%. In sepsis, binding of either pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) among others, induces a complex intracellular signaling system with redundant and complementary activities. Allocetra-OTS (early apoptotic cells) was shown to have a beneficial effect on cytokine storms with downregulation of both anti- and pro-inflammatory cytokines and was prepared from a non-matched donor as described (Mevorach et al. BBMT, 2014) and 140 × 106 cells/kg I.V. in one or two doses were given within 24 hours of diagnosis to 10 patients with sepsis (ClinicalTrials.gov Identifier: NCT03925857).The primary aim was to determine the safety profile and the secondary aims were to determine the preliminary efficacy. Serum cytokine/chemokine and immune modulators measurement was performed sequentially using the Luminex MAGPIX system. Methods, Results & Conclusion All patients were with GCS of at least 13, verbal 5/5, due to the consent requirement. The average Acute Physiology and Chronic Health Evaluation (APACHE) II score was 12.3 (range 8–21) and the average SOFA score upon presentation was 3.4 (range 2–6) in treated patients. All patients fulfilled inclusion and exclusion criteria and met the 2016 definition of sepsis (Singer et al., 2016). All were hospitalized at admission in ICU and experienced a recovery from the septic condition and were discharged alive from the hospital following the resolution of sepsis and completed 28 days of follow-up. No SAEs were reported. No AEs were related to the investigational product. The predicted mortality by the APACHE II score was 18.1% and predicted probability of no death in these 10 patients was 0.15. The predicted mortality by SOFA score at presentation was > 10%, and in 36 matched-historical controls was 27.7%. The study population would have expected to have a mortality rate between 10–27%. Resolution of >20 pro- and anti-inflammatory cytokines was documented. Length of stay in ICU was significantly shorter (p The results of 0% mortality and rapid resolution of sepsis show no safety concerns with a potential preliminary efficacy.