Allogeneic B cell immunomodulatory therapy in amyotrophic lateral sclerosis.

Autor: Sîrbulescu RF; Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Sean M. Healey and AMG Center for ALS, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Nicholson K; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Sean M. Healey and AMG Center for ALS, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Kawai K; Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Hilton OM; Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Sobell D; Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Jin G; Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Verrill DE; Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Dwyer LJ; Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Xiong Y; Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Bachanová P; Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Kim SE; Sean M. Healey and AMG Center for ALS, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Gallup S; Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Gelevski D; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Daley H; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Hernandez Rodriguez DE; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Negre H; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Sturtevant O; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Nikiforow S; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Ritz J; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Chen YB; The Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA., Reeves PM; Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Sluder AE; Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Berry JD; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Sean M. Healey and AMG Center for ALS, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Sadri-Vakili G; Sean M. Healey and AMG Center for ALS, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Cudkowicz M; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Sean M. Healey and AMG Center for ALS, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Poznansky MC; Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.; The Connell and O'Reilly Families Cell Manipulation Core Facility, Dana-Farber Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2024 Jul 15; Vol. 38 (13), pp. e23796.
DOI: 10.1096/fj.202302659R
Abstrakt: Amyotrophic lateral sclerosis (ALS) is an orphan neurodegenerative disease. Immune system dysregulation plays an essential role in ALS onset and progression. Our preclinical studies have shown that the administration of exogenous allogeneic B cells improves outcomes in murine models of skin and brain injury through a process termed pligodraxis, in which B cells adopt an immunoregulatory and neuroprotective phenotype in an injured environment. Here, we investigated the effects of B-cell therapy in the SOD1 G93A mouse preclinical model of ALS and in a person living with ALS. Purified splenic mature naïve B cells from haploidentical donor mice were administered intravenously in SOD1 G93A mice for a total of 10 weekly doses. For the clinical study in a person with advanced ALS, IgA gammopathy of unclear significance, and B lymphopenia, CD19 + B cells were positively selected from a healthy haploidentical donor and infused intravenously twice, at a 60-day interval. Repeated intravenous B-cell administration was safe and significantly delayed disease onset, extended survival, reduced cellular apoptosis, and decreased astrogliosis in SOD1 G93A mice. Repeated B-cell infusion in a person with ALS was safe and did not appear to generate a clinically evident inflammatory response. An improvement of 5 points on the ALSFRS-R scale was observed after the first infusion. Levels of inflammatory markers showed persistent reduction post-infusion. This represents a first demonstration of the efficacy of haploidentical B-cell infusion in the SOD1 G93A mouse and the safety and feasibility of using purified haploidentical B lymphocytes as a cell-based therapeutic strategy for a person with ALS.
(© 2024 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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