Propionate-producing Veillonella parvula regulates the malignant properties of tumor cells of OSCC.

Oral squamous cell carcinoma (OSCC), main head and neck squamous cell carcinomas (HNSCCs), remains a global health concern with unknown pathogenesis. Veillonella parvula NCTC11810 was observed to decrease in saliva microbiome of OSCC patients in this study and the aim was to detect the novel role of Veillonella parvula NCTC11810 in regulating the biological characteristics of OSCC through TROP2/PI3K/Akt pathway. Oral microbial community changes of OSCC patients were detected by 16S rDNA gene sequencing technology. CCK8 assay, Transwell assay, and Annexin V-FITC/PI staining were used for proliferation, invasion, and apoptosis analysis of OSCC cell lines. Expression of proteins were determined by Western blotting analysis. Veillonella parvula NCTC11810 showed decreased in saliva microbiome of TROP2 high-expressed OSCC patients. Culture supernatant of Veillonella parvula NCTC11810 promoted the apoptosis and inhibited the proliferation and invasion ability of HN6 cells, while sodium propionate (SP), the main metabolite of Veillonella parvula NCTC11810, played a similar role through the inhibition of TROP2/PI3K/Akt pathway. Studies above supported the proliferation-inhibiting, invasion-inhibiting, and apoptosis-promoting function of Veillonella parvula NCTC11810 in OSCC cells which provided new insights into oral microbiota and their metabolite as a therapeutic method for OSCC patients with TROP2 high expressing.

Engineering c-Met-CAR NK-92 cells as a promising therapeutic candidate for lung adenocarcinoma.

Mesenchymal-epithelial transition factor (C-Met) has been acknowledged as a significant therapeutic target for treating lung adenocarcinoma (LUAD). However, the potential application of chimeric antigen receptors (CAR)-modified natural killer (NK) cells targeting c-Met in LUAD is rarely explored. In this study, bioinformatic databases were searched and a tissue microarray (TMA) was enrolled to investigate expression status and prognostic role of c-Met in LUAD. Then, four types of c-Met-CAR structures were designed and prepared. The engineering CAR-NK cells containing c-Met-CARs were transfected, verified and characterized. The tumor-inhibitory role of c-Met-CAR-NK cells was finally evaluated in vitro and in vivo. The results demonstrated that c-Met expression elevated and confirmed that high c-Met expression was significantly associated with unfavorable prognosis in LUAD. Then, C-Met-CAR-NK cells were successfully constructed and DAP10 designed in CAR structure was a favorable stimulator for NK cell activation. CCN4 containing DAP10 co-stimulator exhibited the strongest cytotoxicity compared with other CAR-NK cells. Furthermore, CCN4 cells also exerted the prominent tumor-inhibitory effect on xenograft tumor growth. Collectively, this study suggests that DAP10 is a potent stimulator in CAR structure for NK cell activation, and CCN4-based immunotherapy may represent a promising strategy for the treatment of c-Met-positive LUAD.

A SARS-CoV-2 neutralizing antibody discovery by single cell sequencing and molecular modeling.

Although vaccines have been developed, mutations of SARS-CoV-2, especially the dominant B.1.617.2 (delta) and B.1.529 (omicron) strains with more than 30 mutations on their spike protein, have caused a significant decline in prophylaxis, calling for the need for drug improvement. Antibodies are drugs preferentially used in infectious diseases and are easy to get from immunized organisms. The current study combined molecular modeling and single memory B cell sequencing to assess candidate sequences before experiments, providing a strategy for the fabrication of SARS-CoV-2 neutralizing antibodies. A total of 128 sequences were obtained after sequencing 196 memory B cells, and 42 sequences were left after merging extremely similar ones and discarding incomplete ones, followed by homology modeling of the antibody variable region. Thirteen candidate sequences were expressed, of which three were tested positive for receptor binding domain recognition but only one was confirmed as having broad neutralization against several SARS-CoV-2 variants. The current study successfully obtained a SARS-CoV-2 antibody with broad neutralizing abilities and provided a strategy for antibody development in emerging infectious diseases using single memory B cell BCR sequencing and computer assistance in antibody fabrication.