High-Q resonances governed by the quasi-bound states in the continuum in all-dielectric metasurfaces

The realization of high-Q resonances in a silicon metasurface with various broken-symmetry blocks is reported. Theoretical analysis reveals that the sharp resonances in the metasurfaces originate from symmetry-protected bound in the continuum(BIC) and the magnetic dipole dominates these peculiar states. A smaller size of the defect in the broken-symmetry block gives rise to the resonance with a larger Q factor. Importantly, this relationship can be tuned by changing the structural parameter, resulting from the modulation of the topological configuration of BICs. Consequently, a Q factor of more than 3,000 can be easily achieved by optimizing dimensions of the nanostructure. At this sharp resonance, the intensity of the third harmonic generation signal in the patterned structure can be 368 times larger than that of the flat silicon film. The proposed strategy and underlying theory can open up new avenues to realize ultrasharp resonances, which may promote the development of the potential meta-devices for nonlinearity, lasing action, and sensing.

A PD-L1-targeting chimeric switch receptor enhances efficacy of CAR-T cell for pleural and peritoneal metastasis

Pleural and peritoneal metastasis accompanied by malignant pleural effusion(MPE)or malignant ascites(MA)is frequent in patients with advanced solid tumors that originate from the lung,breast,gastrointestinal tract and ovary.Regional delivery of CAR-T cells represents a new strategy to control tumor dissemination in serous cavities.However,malignant effusions constitute an immune-suppressive environment that potentially induces CAR-T cell dysfunction.Here,we demonstrated that the anti-tumor cytotoxicity of conventional 2nd-generation CAR-T cells was significantly inhibited by both the cellular and non-cellular components of MPE/MA,which was primarily attributed to impaired CAR-T cell proliferation and cytokine production in MPE/MA environment.Interestingly,we found that PD-L1 was widely expressed on freshly-isolated MPE/MA cells.Based on this feature,a novel PD-L1-targeting chimeric switch receptor(PD-L1.BB CSR)was designed,which can bind to PD-L1,switching the inhibitory signal into an additional 4-1BB signal.When co-expressed with a 2nd-generation CAR,PD-L1.BB CSR-modified CAR-T cells displayed superior fitness and enhanced functions in both culture medium and MPE/MA environment,causing rapid and durable eradication of pleural and peritoneal metastatic tumors in xenograft models.Further investigations revealed elevated expressions of T-cell activation,proliferation,and cytotoxicity-related genes,and we confirmed that PD-L1 scFv and 4-1BB intracellular domain,the two important components of PD-L1.BB CSR,were both necessary for the functional improvements of CAR-T cells.Overall,our study shed light on the clinical application of PD-L1.BB CSR-modified dual-targeting CAR-T cells.Based on this study,a phase I clinical trial was initiated in patients with pleural or peritoneal metastasis(NCT04684459).