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Efficient adoptive transfer of autologous modified B cells: a new humanized platform mouse model for testing B cells reprogramming therapies

Here, we report a novel experimental setup to perform adoptive transfer of gene-edited B cells using humanized immune system mice by infusing autologous HIS mouse-derived human B cells “educated” in a murine context and thus rendered tolerant to the host. The present approach presents two advantages...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2022-07, Vol.71 (7), p.1771-1775
Main Authors: Page, Audrey, Laurent, Emilie, Nègre, Didier, Costa, Caroline, Pierre, Véronique, Defrance, Thierry, Cosset, François-Loïc, Fusil, Floriane
Format: Article
Language:English
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Summary:Here, we report a novel experimental setup to perform adoptive transfer of gene-edited B cells using humanized immune system mice by infusing autologous HIS mouse-derived human B cells “educated” in a murine context and thus rendered tolerant to the host. The present approach presents two advantages over the conventional humanized PBMC mouse models: (i) it circumvents the risk of xenogeneic graft-versus-host reaction and (ii) it mimics more closely human immune responses, thus favoring clinical translation. We show that the frequencies and numbers of transduced B cells in recipient’s spleens one week post-transfer are within the range of the size of the pre-immune B cell population specific for a given protein antigen in the mouse. They are also compatible with the B cell numbers required to elicit a sizeable immune response upon immunization. Altogether, our findings pave the way for future studies aiming at assessing therapeutic interventions involving B cell reprogramming for instance by an antibody transgene in a “humanized” hematopoietic setting.
ISSN:0340-7004
1432-0851
DOI:10.1007/s00262-021-03101-4