Jiaxuan Yang

Abstract Recently, chimeric antigen receptor (CAR)-T cell therapy has shown great promise in treating haematological malignancies 1–7 . However, CAR-T cell therapy currently has several limitations 8–12 . Here we successfully developed a two-in-one approach to generate non-viral, gene-specific targeted CAR-T cells through CRISPR–Cas9. Using the optimized protocol, we demonstrated feasibility in a preclinical study by inserting an anti-CD19 CAR cassette into the AAVS1 safe-harbour locus. Furthermore, an innovative type of anti-CD19 CAR-T cell with PD1 integration was developed and showed superior ability to eradicate tumour cells in xenograft models. In adoptive therapy for relapsed/refractory aggressive B cell non-Hodgkin lymphoma (ClinicalTrials.gov, NCT04213469 ), we observed a high rate (87.5%) of complete remission and durable responses without serious adverse events in eight patients. Notably, these enhanced CAR-T cells were effective even at a low infusion dose and with a low percentage of CAR + cells. Single-cell analysis showed that the electroporation method resulted in a high percentage of memory T cells in infusion products, and PD1 interference enhanced anti-tumour immune functions, further validating the advantages of non-viral, PD1 -integrated CAR-T cells. Collectively, our results demonstrate the high safety and efficacy of non-viral, gene-specific integrated CAR-T cells, thus providing an innovative technology for CAR-T cell therapy.

, and use it to print luminescent images. The photoluminescence and upconversion luminescence of these images show different patterns and colors under different stimuli. The photostimulated luminescence (PSL) of the printed images causes dynamic changes in appearance and is accordingly applied for dynamic multimodal anticounterfeiting on banknotes. The PSL of these luminescent images is also applied in a virtual war scenario to demonstrate that the dynamic PSL-encrypted information in the fabricated image is sufficiently safe even in extreme cases and that spies will be detected. These results can inspire us with more creative security designs based on this luminescent material.

Abstract Surgical excision is the first choice for clinical cancer therapy. However, major challenges, such as postoperative tumor recurrence and unsatisfactory wound healing after surgery, remain. In this study, an adhesive hydrogel is developed as a multifunctional platform for antitumor chemoimmunotherapy and postoperative wound treatment. The hydrogel adheres firmly to diverse tissues and degrades within 4 weeks in vivo with good histocompatibility. The immune‐stimulating hydrogel ((DOX+R837@HN)@Gel) is fabricated by encapsulating doxorubicin (DOX) and imiquimod‐loaded HSA nanoparticles (R837@HNs) into the hydrogel. When combined with immune checkpoint blockade (ICB) therapy, intratumorally administering (DOX+R837@HN)@Gel exhibits markedly enhanced systemic antitumor efficacy and strengthened antitumor immunity. For tumor surgical resection, (DOX+R837@HN)@Gel can adhere to the wounds and effectively prevents tumor recurrence and achieves long‐term immune memory with ICB therapy. Moreover, the hydrogel achieves rapid hemostasis and promotes wound healing after treating surgical wound models. Therefore, this multifunctional hydrogel has great significance for clinical postsurgical cancer treatment.