The role of activatory and inhibitory FcgR in antibody immunotherapy
Session type: Poster / e-Poster / Silent Theatre session
1Southampton University School of Medicine, UK, 2Leiden University Medical Center, Netherlands
Work to date (both in humans and mouse models) indicates R-expressing effector cells (such as macrophages, neutrophilsgthat Fc and NK cells) are essential for effective antibody immunotherapy. Critically, R can be divided into two types: activating and inhibitory with thegFc relative level of signalling coming from these opposing receptors determining the immune/therapeutic outcome. To explore the role of the activatory R KO and gammagR in immunotherapy, we used a wide array of FcgFc chain KO mice and a selection of different mouse models. Using these models we have shown that immunostimulatory mAb such as anti-CD40 (unlike direct targeting mAb such as anti-Idiotype or anti-CD20 mAb) do not require the R for effective function in vivo. This knowledge allowsgactivatory Fc Rgfor these mAb to be engineered with Fc regions that do not engage Fc thereby reducing potentially unnecessary side-effects resulting from effector cell activation.
To investigate the potential of augmenting existing RIIb) wegantibody therapeutics by blocking the inhibitory receptor (Fc RIIb mAb that are entirely specific and doggenerated a new panel of Fc RIIb mAb fall intogR. These anti-Fcgnot cross-react with other Fc two distinct categories; those which cause tyrosine phosphorylation and subsequent activation of the receptor (stimulatory) and those which block RIIb mAbgreceptor phosphorylation (inhibitory).