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Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable efficacies in treating hematopoietic malignancies, but not in the solid tumors. Incorporating costimulatory signaling domains, such as ICOS or 4-1BB, can positively influence CAR-T cell functions and then the immune responses. These CAR-engineered T cells have showed their enhanced persistence and effector functions with improved antitumor activities, and provided a new approach for the treatment of solid tumors. Here, we designed novel 2nd generation CARs with a costimulatory signaling molecule, dectin-1. The impacts of dectin-1 signaling domain on CAR-T cells were evaluated in vitro and in vivo. Our data show that in vitro cytokine secretions by HER2 or CD19 specific CAR-T cells increase significantly via incorporating this dectin-1 signaling domain. Additional properties of these novel CAR-T cells are affected by this costimulatory domain. Compared with a popular reference (i.e., anti-HER2 CAR-T cells with 4-1BB), in vitro T cell functions and in vivo antitumor activity of the dectin-1 engineered CAR-T cells are similar to the 4-1BB based, and both are discrete to the mock T cells. Furthermore, we found that the CAR-T cells with dectin-1 show distinct phenotype and exhaustion marker expression. These collective results suggest that the incorporation of this new signaling domain, dectin-1, into the CARs may provide the clinical potential of the CAR-T cells through this signaling domain in treating solid tumors.

There are two opposite mechanisms for the growth of anodic TiO2nanotubes. One is the field-assisted dissolution and ejection theory, the other is the oxygen bubble mold. In order to prove the latter mechanism is right, we constructed a three-layer nanotube structure (upper layer nanotubes + dense oxide film + lower layer nanotubes), which was obtained by three steps anodization. The upper and lower layers nanotubes are separated by a dense oxide film. When the dense oxide film is thin, the lower layer nanotubes is longer than the upper layer nanotubes. On the contrary, when the dense oxide film is thick, the lower layer nanotubes is shorter than the upper layer nanotubes. In either case, the anodization conditions of the upper and lower layer nanotubes are the same. This could not be explained by field-assisted dissolution theory. By analyzing the curve, we introduce a new method to decide the time of entering the third stage of the anodization, which is the main stage of nanotubes growth. With the second anodization voltage increases, the time edge entering the third stage become longer, which means the time to growth the nanotubes becomes shorter, and finally leading the different length of the nanotubes.