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

Audrey Page (1) , Emilie Laurent (1) , Didier Nègre (2, 1) , Caroline Costa (1) , Véronique Pierre (1) , Thierry Defrance (1) , François-Loïc Cosset (1) , Floriane Fusil (1)

1 CIRI - Centre International de Recherche en Infectiologie
2 CNRS - Centre National de la Recherche Scientifique

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.

Mots clés: Humanized immune system; B cell adoptive transfer; Cell therapy; Gene therapy

Domaines: Sciences du Vivant [q-bio]

Audrey Page, Emilie Laurent, Didier Nègre, Caroline Costa, Véronique Pierre, et al.. Efficient adoptive transfer of autologous modified B cells: a new humanized platform mouse model for testing B cells reprogramming therapies. Cancer Immunology, Immunotherapy, 2021, ⟨10.1007/s00262-021-03101-4⟩. ⟨hal-03428459⟩