Controlling CAR-T cell activity and specificity with synthetic SparX adapters.

While conventional chimeric antigen-receptor (CAR)-T therapies have shown remarkable clinical activity in some settings, they can induce severe toxicities and are rarely curative. To address these challenges, we developed a controllable cell therapy where synthetic D-domain-containing proteins (soluble protein antigen-receptor X-linker [SparX]) bind one or more tumor antigens and mark those cells for elimination by genetically modified T cells (antigen-receptor complex [ARC]-T). The chimeric antigen receptor was engineered with a D-domain that specifically binds to the SparX protein via a unique TAG, derived from human alpha-fetoprotein.

Relebactam restores susceptibility of resistant Pseudomonas aeruginosa and Enterobacterales and enhances imipenem activity against chromosomal AmpC-producing species: analysis of global SMART 2018-2020.

Background: Carbapenem-resistant bacteria are an increasing problem in clinical practice; thus, it is important to identify β-lactamase inhibitors (e.g., relebactam) that can restore carbapenem susceptibility.

Conceptualizing the human drivers of low tree diversity in planted urban landscapes.

Despite the abundance of tree diversity in the natural world, and generally high tree species richness in urban areas, urban forests continue to be dominated by a limited number of species. As socio-ecological systems, urban forests are shaped by historical and current management efforts and decision-making across a wide range of human actors. Drawing on past research, we offer a conceptual framework for describing the complex interactions among tree producers and consumers as trees are selected, grown, specified, and planted in private and public urban areas.

Preclinical Efficacy of BCMA-Directed CAR T Cells Incorporating a Novel D Domain Antigen Recognition Domain.

Chimeric antigen receptor (CAR) T-cell therapies directed against B-cell maturation antigen (BCMA) have shown compelling clinical activity and manageable safety in subjects with relapsed and refractory multiple myeloma (RRMM). Prior reported CAR T cells have mostly used antibody fragments such as humanized or murine single-chain variable fragments or camelid heavy-chain antibody fragments as the antigen recognition motif. Herein, we describe the generation and preclinical evaluation of ddBCMA CAR, which uses a novel BCMA binding domain discovered from our D domain phage display libraries and incorporates a 4-1BB costimulatory motif and CD3-zeta T-cell activation domain.

Incidence of Venous Thromboembolism in Patients Receiving Anticoagulation for Foot and Ankle Surgery.

Venous thromboembolism (VTE) is a serious medical condition that can be an unfortunate complication arising from foot and ankle surgery. Many factors may predispose a patient to a VTE event including prolonged postoperative immobilization, comorbidities, extended length of tourniquet time, and higher risk surgeries. Unfortunately, there is no clinical consensus for guidelines on VTE prophylaxis following foot and ankle surgery.