RESUMEN
Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.
RESUMEN
Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.
RESUMEN
BACKGROUND:Condylar fracture can occur under direct and indirect forces, and however, its risk and correlation with the impact site are rarely reported. OBJECTIVE:To quickly establish normal mandible three-dimensional finite element model and to analyze the strain conditions of the condyle under force at different parts of the mandible. METHODS: An adolescent volunteer was examined by multilayer spiral CT scans, whose mandible was normal and oral cavity was healthy. We used the reverse engineering software Mimics and large finite element software MSC.Patran to establish the three-dimensional finite element model of the mandible and to verify the feasibility of the model in the impact test at the body of the mandible, chin, mandibular angle and condyle. RESULTS AND CONCLUSION:A rapid establishment of mandible dimensional finite element biomechanical model could reproduce the morphology of the mandible, which was able to obtain the overal visual impression of the mandibular condyle. Geometric model included 80 044 nodes and 18 441 units. The mandibular chin, one side of the body, mandibular angle and condyle were given 100 N force respectively. The maximum equivalent stress of the bone cortex appeared in condylar region. So the mandibular condylar fractures were at the greatest risk. Experimental results contribute to mechanicaly analyze the condylar fracture type and to judge the severity of fractures.