Immunotherapy targeting inhibitory Fc? receptor IIB (CD32b) in the mouse is limited by monoclonal antibody consumption and receptor internalization

Genetic deficiency of the inhibitory Fc receptor, Fc?RIIB (CD32b), has been shown to augment the activity of activatory Fc?R and promote mAb immunotherapy. To investigate whether mAbs capable of blocking Fc?RIIB have similar capacity, we recently generated a panel of specific anti-mouse Fc?RIIB mAbs that do not cross-react with other FcRs, allowing us to study the potential of Fc?RIIB as a therapeutic target. Previous work revealed a number of these mAbs capable of eliciting programmed cell death of targets, and in the present study we demonstrated their ability to promote target cell phagocytosis. However, in a variety of murine tumor models, anti-Fc?RIIB mAbs demonstrated limited therapeutic activity despite optimized treatment regimens. Unexpectedly, we observed that the anti-Fc?RIIB mAbs are rapidly and extensively consumed in vivo, both by the tumor and host cells, including B cells, leading to a precipitous loss from the circulation. Closer analysis revealed that the anti-Fc?RIIB mAbs become extensively internalized from the cell surface within 24 h in vivo, likely explaining their suboptimal efficacy. Subsequent studies revealed that anti-Fc?RIIB mAb immunotherapy was effective when used against Fc?RIIB+ tumors in Fc?RIIB?/? recipients, indicating that consumption of the mAb by nontumor cells is the primary limitation of these reagents. Importantly, similar rates of internalization were not seen on human target cells, at least in vitro. These studies further highlight the need to determine the propensity of mAb therapeutics to internalize target receptors and also identify potential key differences between human and mouse cells in this respect

Silicified Mississippian Brachiopods from Muhua, Southern China: Rhynchonellides, Athyridides, Spiriferides, Spiriferinides, and Terebratulides

The second part of the monograph of the silicified brachiopod fauna from the Muhua Formation concludes with the descriptions of 36 species belonging to 32 genera and 22 families. Eighteen species are reported in open nomenclature. Two new rhynchonellide species are described: Coledium bruntoni sp. nov. and Pleuropugnoides calcaris sp. nov. The described brachiopod fauna is dominated by spiriferides (16 species), rhynchonellides (9 species), and athyridides (7 species), while spiriferinides and terebratulides are represented by 1 and 3 species, respectively. The brachiopod fauna from the Muhua Formation is characterised by remarkably high species diversity. Together with those species described in the first part of the monograph the fauna includes 69 species. The study of the brachiopod faunal dynamics during the late Famennian-late Tournaisian in southern China reveals that after a decline in the generic diversity at the Devonian-Carboniferous boundary (D C boundary event), the Early Tournaisian brachiopod fauna shows slight impoverishment. In the middle Tournaisian the brachiopod fauna from South China shows an explosive increase in diversity on generic level which is well exemplified by the material from Muhua. The brachiopod fauna from the Muhua Formation represents a fully recovered high diversity fauna consisting of forms representing a wide spectrum of attachment strategies as well as highly specialised forms (e.g., micromorphs) adapted to special kinds of ecological niches. Numerous evidence of the biotic interaction between brachiopods and other co-occurring fauna have been revealed in the material from Muhua. These are drill holes of predatory origin, borings made on dead shells as post-mortem infestation, shell damages and malformations, and parasitic infestations.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000299303900012&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701PaleontologySCI(E)6ARTICLE4793-8425