Induced pluripotent stem-cell-derived CD19-directed chimeric antigen receptor natural killer cells in B-cell lymphoma: a phase 1, first-in-human trial.

Background: FT596 is an induced pluripotent stem-cell (iPSC)-derived chimeric antigen receptor (CAR) natural killer (NK) cell therapy with three antitumour modalities: a CD19 CAR; a high-affinity, non-cleavable CD16 Fc receptor; and interleukin-15-interleukin-15 receptor fusion. In this study, we aimed to determine the recommended phase 2 dose (RP2D) and evaluate the safety and tolerability of FT596 as monotherapy and in combination with rituximab. We also aimed to evaluate the antitumour activity and characterise the pharmacokinetics of FT596 as monotherapy and in combination with rituximab.

Antibody-drug conjugates targeting SSEA-4 inhibits growth and migration of SSEA-4 positive breast cancer cells.

Although breast cancer treatment has evolved significantly in recent years, drug resistance remains a major challenge. To identify new targets for breast cancer, we found that stage-specific embryonic antigen 4 (SSEA-4) is expressed in all subtypes of breast cancer cell lines, and the increased expression of the associated enzymes β3GalT5 and ST3Gal2 correlates with poor recurrence-free survival (RFS) in breast cancer. We also found that SSEA-4 antibodies can be rapidly internalized into breast cancer cells, a property that makes SSEA-4 an attractive target for antibody-drug conjugates (ADCs).

DYRK1A-TGF-β signaling axis determines sensitivity to OXPHOS inhibition in hepatocellular carcinoma.

Intervening in mitochondrial oxidative phosphorylation (OXPHOS) has emerged as a potential therapeutic strategy for certain types of cancers. Employing kinome-based CRISPR screen, we find that knockout of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) synergizes with OXPHOS inhibitor IACS-010759 in liver cancer cells. Targeting DYRK1A combined with OXPHOS inhibitors activates TGF-β signaling, which is crucial for OXPHOS-inhibition-triggered cell death.

Akkermansia muciniphila inhibits jejunal lipid absorption and regulates jejunal core bacteria.

Insufficiency of Akkermansia muciniphila (Akk) has been implicated in the pathogenesis of metabolic diseases, and administration or restoration of Akk has ameliorated these disorders. Recently, Pasteurized Akk (PA-Akk) has been approved as a functional food. However, the impact of Akk on lipid absorption in the proximal intestine, which is directly exposed to orally administered Akk, remains largely unexplored.

Bronchiectasis Exacerbation Increases the Risk of Adverse Renal Outcomes-Results From a Large Territory-Wide Cohort Study.

Introduction: Bronchiectasis exacerbation (BE) is associated with unfavorable sequelae in other organs such as the cardiovascular system; data regarding its impact on adverse term renal outcomes, however, is lacking.

Methods: A territory-wide retrospective cohort study was conducted in Hong Kong between 1/1/1993 and 31/12/2017. All patients with bronchiectasis followed in the public healthcare system in 2017 were classified as "Exacerbators" or "Non-Exacerbators," and their adverse renal outcomes (renal progression [decrease in eGFR by 30 mL/min lasted for more than 12 months during follow up], acute kidney injury [AKI], and annual rate of eGFR decline) in the ensuing 7 years were compared.