Ankri, C.; Hershkovitz, O.; Hershkovitz, L.; Brami, M.; Levy, R.; Sarig, H.; Souli, E.; Reicher, B.; Amor-Baroukh, V.; Mevorach, D.; Nyska, A. Safety of Repeated Administration of Xenogeneic Human Apoptotic State (Allocetra-OTS) in Sprague Dawley Rats. Pharmaceutics2024, 16, 426.
Ankri, C.; Hershkovitz, O.; Hershkovitz, L.; Brami, M.; Levy, R.; Sarig, H.; Souli, E.; Reicher, B.; Amor-Baroukh, V.; Mevorach, D.; Nyska, A. Safety of Repeated Administration of Xenogeneic Human Apoptotic State (Allocetra-OTS) in Sprague Dawley Rats. Pharmaceutics 2024, 16, 426.
Ankri, C.; Hershkovitz, O.; Hershkovitz, L.; Brami, M.; Levy, R.; Sarig, H.; Souli, E.; Reicher, B.; Amor-Baroukh, V.; Mevorach, D.; Nyska, A. Safety of Repeated Administration of Xenogeneic Human Apoptotic State (Allocetra-OTS) in Sprague Dawley Rats. Pharmaceutics2024, 16, 426.
Ankri, C.; Hershkovitz, O.; Hershkovitz, L.; Brami, M.; Levy, R.; Sarig, H.; Souli, E.; Reicher, B.; Amor-Baroukh, V.; Mevorach, D.; Nyska, A. Safety of Repeated Administration of Xenogeneic Human Apoptotic State (Allocetra-OTS) in Sprague Dawley Rats. Pharmaceutics 2024, 16, 426.
Abstract
Apoptotic cells possess immunomodulatory effects that can be utilized to treat imbalanced immune conditions. Information on the preclinical safety of such treatment is sparse. In this study, the safety of apoptotic cells (Allocetra-OTS) was assessed in a GLP toxicological study on Sprague Dawley rats. Three doses of Allocetra-OTS or vehicle were administered intravenously (IV) for 3 consecutive days. Animals in the Main study were sacrificed on day 4, while animals from the Recovery groups were kept for 14 or 28 days. Allocetra-OTS was well tolerated, and no adverse effects were observed in body weight, clinical signs, food consumption or ophthalmologic observation. Thus, the No Observed Adverse Effect Level (NOAEL) dose was determined as the highest dose administered. An observed elevation in immune cells was suspected to be due to Allocetra-OTS; similarly to other clinical chemistry parameters, however, it was resolved in the Recovery phases. Splenomegaly and a dose-related Extramedullary Hematopoiesis (EMH) in the red pulp were observed, with no adverse events, and were considered to be a normal and expected reaction following IV administration of cell-based therapies. In conclusion, under the conditions of this study Allocetra-OTS was concluded to be safe, further supporting its potential candidacy for clinical studies
Keywords
cell-based therapies; human apoptotic cells; PBMC; safety
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
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