T lymphocytes expressing the switchable chimeric Fc receptor CD64 exhibit augmented persistence and antitumor activity.

Chimeric antigen receptor (CAR) T cell therapy lacks persistent efficacy with "on-target, off-tumor" toxicities for treating solid tumors. Thus, an antibody-guided switchable CAR vector, the chimeric Fc receptor CD64 (CFR64), composed of a CD64 extracellular domain, is designed. T cells expressing CFR64 exert more robust cytotoxicity against cancer cells than CFR T cells with high-affinity CD16 variant (CD16v) or CD32A as their extracellular domains. CFR64 T cells also exhibit better long-term cytotoxicity and resistance to T cell exhaustion compared with conventional CAR T cells. With trastuzumab, the immunological synapse (IS) established by CFR64 is more stable with lower intensity induction of downstream signaling than anti-HER2 CAR T cells. Moreover, CFR64 T cells exhibit fused mitochondria in response to stimulation, while CARH2 T cells contain predominantly punctate mitochondria. These results show that CFR64 T cells may serve as a controllable engineered T cell therapy with prolonged persistence and long-term antitumor activity.

Co-expression of a PD-L1-specific chimeric switch receptor augments the efficacy and persistence of CAR T cells via the CD70-CD27 axis.

Co-expression of chimeric switch receptors (CSRs) specific for PD-L1 improves the antitumor effects of chimeric antigen receptor (CAR) T cells. However, the effects of trans-recognition between CSRs and PD-L1 expressed by activated CAR T cells remain unclear. Here, we design a CSR specific for PD-L1 (CARP), containing the transmembrane and cytoplasmic signaling domains of CD28 but not the CD3 ζ chain. We show that CARP T cells enhance the antitumor activity of anti-mesothelin CAR (CARMz) T cells in vitro and in vivo. In addition, confocal microscopy indicates that PD-L1 molecules on CARMz T cells accumulate at cell-cell contacts with CARP T cells. Using single-cell RNA-sequencing analysis, we reveal that CARP T cells promote CARMz T cells differentiation into central memory-like T cells, upregulate genes related to Th1 cells, and downregulate Th2-associated cytokines through the CD70-CD27 axis. Moreover, these effects are not restricted to PD-L1, as CAR19 T cells expressing anti-CD19 CSR exhibit similar effects on anti-PSCA CAR T cells with truncated CD19 expression. These findings suggest that target trans-recognition by CSRs on CAR T cells may improve the efficacy and persistence of CAR T cells via the CD70-CD27 axis.

Proteome profile of bovine ruminal epithelial tissue based on GeLC-MS/MS.

The proteome of rumen epithelial tissue was analysed by SDS-PAGE coupled with LC-MS/MS. 813 non-redundant proteins were identified of which 7.4 % featured membrane-spanning domains and 15.4 % harboured a signal peptide. According to the gene ontology annotation, the most abundant proteins exhibited binding activities related to their molecular functions, were proteins of cellular components or belonged to various metabolic processes. A predominant group of canonical pathways in the rumen epithelial tissue was identified using the IPA software. The GeLC-MS/MS approach was used to characterise the entire protein expression repertoire in rumen tissue, providing a more detailed understanding of the important biological processes in the rumen.

Impact of region on the composition of milk fatty acids in China.

BACKGROUND: Milk composition and its fatty acid profile have received much attention with respect to improving human health. However, limited work has been conducted to assess the composition of milk fat in China, which is the third largest producer of milk in the world. In this study the effects of geographical region and seasonal changes (spring and summer) on the fatty acid composition of milk samples collected from six Chinese farms were investigated. RESULTS: Milk fat and protein contents, as well as some individual fatty acids and five fatty acid groups, were found to be unaffected by season, but they did show significant differences by geographical region. Levels of milk cis-9, trans-11 conjugated linoleic acid decreased in summer and increased in spring, increased in north (Hohhot), northeast (Harbin), north centre (Beijing) and northwest (Xi'an) China and decreased in far northwest (Urumqi) and east (Chuzhou) China. Monounsaturated fatty acids increased in east and northwest China and decreased in northeast China, while polyunsaturated fatty acids increased in far northwest and north centre China and decreased in northeast China. CONCLUSION: This study provides relevent information that contributes to the understanding of parameters affecting variability of milk fatty acid profiles.