Developing ROR1 Targeting CAR-T Cells against Solid Tumors in Preclinical Studies.

Chimeric antigen receptor (CAR)-modified T-cells (CAR-T) have demonstrated promising clinical benefits against B-cell malignancies. Yet, its application for solid tumors is still facing challenges. Unlike haematological cancers, solid tumors often lack good targets, which are ideally expressed on the tumor cells, but not by the normal healthy cells. Fortunately, receptor tyrosine kinase-like orphan receptor 1 (ROR1) is among a few good cancer targets that is aberrantly expressed on various tumors but has a low expression on normal tissue, suggesting it as a good candidate for CAR-T therapy. Here, we constructed two ROR1 CARs with the same antigen recognition domain that was derived from Zilovertamab but differing in hinge regions. Both CARs target ROR1+ cancer cells specifically, but CAR with a shorter IgG4 hinge exhibits a higher surface expression and better in vitro functionality. We further tested the ROR1 CAR-T in three human solid tumor xenografted mouse models. Our ROR1 CAR-T cells controlled the solid tumor growth without causing any severe toxicity. Our results demonstrated that ROR1 CAR-T derived from Zilovertamab is efficacious and safe to suppress ROR1+ solid tumors in vitro and in vivo, providing a promising therapeutic option for future clinical application.

Modelling noise annoyance responses to combined sound sources and views of sea, road traffic, and mountain greenery.

This paper studies the effect of human perception of visual and audio settings in an urban environment on annoyance. Video clips were projected onto a window panel of a living room to simulate neighborhood views containing different percentages of sea, mountain greenery, and road. These video clips were combined with audio stimuli corresponding to the congruent traffic and sea sounds. 246 participants were presented with 11 audio-visual stimuli and requested to respond to questions after the presentation. The collected responses were used to formulate a multivariate ordered logit model to predict the probability of evoking a high annoyance response. The findings revealed that views embracing mountain greenery close-by could enhance annoyance, which is contrary to other findings that greenery could always moderate noise annoyance. In addition, a 60% sea view was found to be able to yield 1 dB equivalent reduction in total sound pressure level. The trade-off was comparable to that achieved by having sea sound at a level 5 dB higher than road traffic noise. Exposure to road traffic noise level being 3 dB higher than sea sound level (i.e., signal-to-noise ratio = -3) together with a 60% sea view could provide an additional 1.5 dB equivalent reduction.