Membrane-Proximal Epitope Facilitates Efficient T Cell Synapse Formation by Anti-FcRH5/CD3 and Is a Requirement for Myeloma Cell Killing

The anti-FcRH5/CD3 T cell-dependent bispecific antibody (TDB) targets the B cell lineage marker FcRH5 expressed in multiple myeloma (MM) tumor cells. We demonstrate that TDBs trigger T cell receptor activation by inducing target clustering and exclusion of CD45 phosphatase from the synapse. The dimensions of the target molecule play a key role in the efficiency of the synapse formation. The anti-FcRH5/CD3 TDB kills human plasma cells and patient-derived myeloma cells at picomolar concentrations and results in complete depletion of B cells and bone marrow plasma cells in cynomolgus monkeys. These data demonstrate the potential for the anti-FcRH5/CD3 TDB, alone or in combination with inhibition of PD-1/PD-L1 signaling, in the treatment of MM and other B cell malignancies.This work was supported by a Sir Henry Dale Fellowship (J.R.J.) jointly funded by the Wellcome Trust and the Royal Society (grant number: 099966/Z/12/Z). PhD studentships (S.A.M. and M.J.H.) were funded by the Wellcome Trust (grant number: 102195/Z/13/Z)

Effects of degree and timing of social housing on reversal learning and response to novel objects in dairy calves

Rodents and primates deprived of early social contact exhibit deficits in learning and behavioural flexibility. They often also exhibit apparent signs of elevated anxiety, although the relationship between these effects has not been studied. To investigate whether dairy calves are similarly affected, we first compared calves housed in standard individual pens (n = 7) to those housed in a dynamic group with access to their mothers (n = 8). All calves learned to approach the correct stimulus in a visual discrimination task. Only one individually housed calf was able to re-learn the task when the stimuli were reversed, compared to all but one calf from the group. A second experiment investigated whether this effect might be explained by anxiety in individually housed animals interfering with their learning, and tested varying degrees of social contact in addition to the complex group: pair housing beginning early (approximately 6 days old) and late (6 weeks old). Again, fewer individually reared calves learned the reversal task (2 of 10 or 20%) compared to early paired and grouped calves (16 of 21 or 76% of calves). Late paired calves had intermediate success. Individually housed calves were slower to touch novel objects, but the magnitude of the fear response did not correlate with reversal performance. We conclude that individually housed calves have learning deficits, but these deficits were not likely associated with increased anxiety

A human endothelial cell-based recycling assay for screening of FcRn targeted molecules

Albumin and IgG have remarkably long serum half-lives due to pH-dependent FcRn-mediated cellular recycling that rescues both ligands from intracellular degradation. Furthermore, increase in half-lives of IgG and albumin-based therapeutics has the potential to improve their efficacies, but there is a great need for robust methods for screening of relative FcRn-dependent recycling ability. Here, we report on a novel human endothelial cell-based recycling assay (HERA) that can be used for such pre-clinical screening. In HERA, rescue from degradation depends on FcRn, and engineered ligands are recycled in a manner that correlates with their half-lives in human FcRn transgenic mice. Thus, HERA is a novel cellular assay that can be used to predict how FcRn-binding proteins are rescued from intracellular degradation

Farm animal welfare influences on markets and consumer attitudes in Latin America: the cases of Mexico, Chile and Brazil

In recent years, animal welfare has become an important element of sustainable production that has evolved along with the transformation of animal production systems. Consumer attitudes towards farm animal welfare are changing around the world, especially at emerging markets of Asia, Africa and Latin America. Survey-based research on consumer attitudes towards farm animal welfare has increased. However, the geographical coverage of studies on consumer attitudes and perceptions about farm animal welfare has mostly been limited to Europe, and North America. Until now, Latin American consumers' attitudes towards animal welfare have not been well studied. Despite the fact that Mexico, Chile and Brazil belong to the same region (according to international organizations), there are marked differences between these countries in terms of their economical and geographical characteristics among other factors. Those differences potentially have an impact on consumer attitudes towards animal welfare and livestock production systems in general. Given the evidence from the literature review, it seems advisable that Latin American producers and food industry who engage in animal welfare-enhancing practices should clearly label their products with information on the type of husbandry system to reach those consumers who want to make an informed choice. Therefore, there are some aspects that need to be studied and cannot be worked separately in order to promote and understand consumer attitudes towards dairy and beef systems, such as geography, economic development, and politics.Vicerrectoria de Investigacion of the Pontificia Universidad Catolica de Chile, Concurso Estadias y Pasantias Breves EPB16008 Facultad de Agronomia e Ingenieria Forestal of the Pontificia Universidad Catolica de Chil