Humanized tau antibodies promote tau uptake by human microglia without any increase of inflammation
Posted on 2020-05-30 - 03:45
Abstract Immunotherapies targeting pathological tau have recently emerged as a promising approach for treatment of neurodegenerative disorders. We have previously showed that the mouse antibody DC8E8 discriminates between healthy and pathological tau, reduces tau pathology in murine tauopathy models and inhibits neuronal internalization of AD tau species in vitro. Here we show, that DC8E8 and antibodies elicited against the first-in-man tau vaccine, AADvac1, which is based on the DC8E8 epitope peptide, both promote uptake of pathological tau by mouse primary microglia. IgG1 and IgG4 isotypes of AX004, the humanized versions of DC8E8, accelerate tau uptake by human primary microglia isolated from post-mortem aged and diseased brains. This promoting activity requires the presence of the Fc-domain of the antibodies. The IgG1 isotype of AX004 showed greater ability to promote tau uptake compared to the IgG4 isotype, while none of the antibody-tau complexes provoked increased pro-inflammatory activity of microglia. Our data suggest that IgG1 has better suitability for therapeutic development.
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Zilkova, Monika; Nolle, Anna; Kovacech, Branislav; Kontsekova, Eva; Weisova, Petronela; Filipcik, Peter; et al. (2020). Humanized tau antibodies promote tau uptake by human microglia without any increase of inflammation. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.5000318.v1
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AUTHORS (15)
MZ
Monika Zilkova
AN
Anna Nolle
BK
Branislav Kovacech
EK
Eva Kontsekova
PW
Petronela Weisova
PF
Peter Filipcik
RS
Rostislav Skrabana
MP
Michal Prcina
TH
Tomas Hromadka
OC
Ondrej Cehlar
GR
Gabriela Paulikova Rolkova
DM
Denisa Maderova
MN
Michal Novak
NZ
Norbert Zilka
JH
Jeroen J. M. Hoozemans