{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:40:39Z","timestamp":1785307239609,"version":"3.55.0"},"reference-count":60,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T00:00:00Z","timestamp":1710892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Enlivex Therapeutics Ltd. Ness-Ziona, Israel"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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 terms of 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 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 the 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics16030426","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T05:56:07Z","timestamp":1710914167000},"page":"426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Safety of Repeated Administration of Xenogeneic Human Apoptotic State (Allocetra-OTS) in Sprague Dawley Rats"],"prefix":"10.3390","volume":"16","author":[{"given":"Chen","family":"Ankri","sequence":"first","affiliation":[{"name":"Enlivex Therapeutics Ltd., Ness Ziona 7403618, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oren","family":"Hershkovitz","sequence":"additional","affiliation":[{"name":"Enlivex Therapeutics Ltd., Ness Ziona 7403618, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liat","family":"Hershkovitz","sequence":"additional","affiliation":[{"name":"Independent Researcher, Revadim 798200, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meital","family":"Brami","sequence":"additional","affiliation":[{"name":"Pharmaseed Ltd., Ness Ziona 7404709, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronnie","family":"Levy","sequence":"additional","affiliation":[{"name":"Pharmaseed Ltd., Ness Ziona 7404709, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadar","family":"Sarig","sequence":"additional","affiliation":[{"name":"Pharmaseed Ltd., Ness Ziona 7404709, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Einat","family":"Souli","sequence":"additional","affiliation":[{"name":"Pharmaseed Ltd., Ness Ziona 7404709, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barak","family":"Reicher","sequence":"additional","affiliation":[{"name":"Enlivex Therapeutics Ltd., Ness Ziona 7403618, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique","family":"Amor-Baroukh","sequence":"additional","affiliation":[{"name":"Enlivex Therapeutics Ltd., Ness Ziona 7403618, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dror","family":"Mevorach","sequence":"additional","affiliation":[{"name":"Enlivex Therapeutics Ltd., Ness Ziona 7403618, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7847-2513","authenticated-orcid":false,"given":"Abraham","family":"Nyska","sequence":"additional","affiliation":[{"name":"Sackler School of Medicine, Tel Aviv University, Tel Aviv 6139001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.bbmt.2013.10.010","article-title":"Single Infusion of Donor Mononuclear Early Apoptotic Cells as Prophylaxis for Graft-versus-Host Disease in Myeloablative HLA-Matched Allogeneic Bone Marrow Transplantation: A Phase I\/IIa Clinical Trial","volume":"20","author":"Mevorach","year":"2014","journal-title":"Biol. 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