biostudies-literatureCastiello MCIntramural NIH HHSMinistero dell’Istruzione, dell’Università e della RicercaDivision of Intramural Research, National Institute of Allergy and Infectious Diseases309-320.e6https://www.ebi.ac.uk/biostudies/studies/S-EPMC8322962biostudies-literatureUnknown147(1)<h4>Background</h4>Mutations in the recombinase-activating genes cause severe immunodeficiency, with a spectrum of phenotypes ranging from severe combined immunodeficiency to immune dysregulation. Hematopoietic stem cell transplantation is the only curative option, but a high risk of graft failure and poor immune reconstitution have been observed in the absence of myeloablation.<h4>Objectives</h4>Our aim was to improve multilineage engraftment; we tested nongenotoxic conditioning with anti-CD45 mAbs conjugated with saporin CD45 (CD45-SAP).<h4>Methods</h4>Rag1-KO and Rag1-F971L mice, which represent models of severe combined immune deficiency and combined immune deficiency with immune dysregulation, respectively, were conditioned with CD45-SAP, CD45-SAP plus 2 Gy of total body irradiation (The Journal of allergy and clinical immunologyEfficacy and safety of anti-CD45-saporin as conditioning agent for RAG deficiency.PMC8322962ZIA AI001222Castiello MCVilla ABosticardo MFontana ECorsino CNotarangelo LDSereni LYamazaki YSacchetti NUva PPalchaudhuri RCalzoni EScadden DTBortolomai IDraghici EYu HHfalseEfficacy and safety of anti-CD45-saporin as conditioning agent for RAG deficiency.<h4>Background</h4>Mutations in the recombinase-activating genes cause severe immunodeficiency, with a spectrum of phenotypes ranging from severe combined immunodeficiency to immune dysregulation. Hematopoietic stem cell transplantation is the only curative option, but a high risk of graft failure and poor immune reconstitution have been observed in the absence of myeloablation.<h4>Objectives</h4>Our aim was to improve multilineage engraftment; we tested nongenotoxic conditioning with anti-CD45 mAbs conjugated with saporin CD45 (CD45-SAP).<h4>Methods</h4>Rag1-KO and Rag1-F971L mice, which represent models of severe combined immune deficiency and combined immune deficiency with immune dysregulation, respectively, were conditioned with CD45-SAP, CD45-SAP plus 2 Gy of total body irradiation (2021-01-01T00:00:00Z2021 Jan2026-05-09T17:15:27.849Z2022-02-11T00:53:19.1ZS-EPMC83229623238710910.1016/j.jaci.2020.04.033