Although chimeric antigen receptor (CAR)-engineered T cells have shown great success in the treatment of B cell malignancies, this strategy has limited efficacy in patients with solid tumors. In mouse CAR-T cells, IL-7 and CCL19 expression have been demonstrated to improve T cell infiltration and CAR-T cell survival in mouse tumors. Therefore, in the current study, we engineered human CAR-T cells to secrete human IL-7 and CCL19 (7 × 19) and found that these 7 × 19 CAR-T cells showed enhanced capacities of expansion and migration in vitro. Furthermore, 7 × 19 CAR-T cells showed superior tumor suppression ability compared to conventional CAR-T cells in xenografts of hepatocellular carcinoma (HCC) cell lines, primary HCC tissue samples and pancreatic carcinoma (PC) cell lines. We then initiated a phase 1 clinical trial in advanced HCC/PC/ovarian carcinoma (OC) patients with glypican-3 (GPC3) or mesothelin (MSLN) expression. In a patient with advanced HCC, anti-GPC3-7 × 19 CAR-T treatment resulted in complete tumor disappearance 30 days post intratumor injection. In a patient with advanced PC, anti-MSLN-7 × 19 CAR-T treatment resulted in almost complete tumor disappearance 240 days post-intravenous infusion. Our results demonstrated that the incorporation of 7 × 19 into CAR-T cells significantly enhanced the antitumor activity against human solid tumor. Trial registration: NCT03198546. Registered 26 June 2017, https://clinicaltrials.gov/ct2/show/NCT03198546?term=NCT03198546&draw=2&rank=1

Background Gastric cancer (GC) is a common cancer in Asia and currently lacks a targeted therapy approach. Mesothelin (MSLN) has been reported to be expressed in GC tissue and could be targeted by chimeric antigen receptor (CAR) T cells. Mesothelin targeting CAR-T has been reported in mesothelioma, lung cancer, breast cancer, and pancreas cancer. However, the feasibility of using anti-MSLN CAR T cells to treat GC remains to be studied. Methods We verified MSLN expression in primary human GC tissues and GC cell lines and then redirected T cells with a CAR containing the MSLN scFv (single-chain variable fragment), CD3ζ, CD28, and DAP10 intracellular signaling domain (M28z10) to target MSLN. We evaluated the function of these CAR T cells in vitro in terms of cytotoxicity, cytokine secretion, and surface phenotype changes when they encountered MSLN+ GC cells. We also established four different xenograft GC mouse models to assess in vivo antitumor activity. Results M28z10 T cells exhibited strong cytotoxicity and cytokine-secreting ability against GC cells in vitro. In addition, cell surface phenotyping suggested significant activation of M28z10 T cells upon target cell stimulation. M28z10 T cells induced GC regression in different xenograft mouse models and prolonged the survival of these mice compared with GFP-transduced T cells in the intraperitoneal and pulmonary metastatic GC models. Importantly, peritumoral delivery strategy can lead to improved CAR-T cells infiltration into tumor tissue and significantly suppress the growth of GC in a subcutaneous GC model. Conclusion These results demonstrate that M28z10 T cells possess strong antitumor activity and represent a promising therapeutic approach to GC.

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Great endeavors have been dedicated to the development of wound dressing materials. However, there is still a demand for developing a wound dressing hydrogel that integrates natural macromolecules without requiring extra chemical modifications, so as to enable a facile transformation and practical application in wound healing. Herein, a composite hydrogel was prepared with water-soluble polysaccharides from Enteromorpha prolifera (PEP) cross-linked with boric acid and polyacrylamide cross-linked via polymerization (PAM) using a one-pot method. The dual-network of this hydrogel enabled it to have an ultratough mechanical strength. Moreover, interfacial characterizations reflected that the hydrogen bonds and dynamic hydroxyl−borate bonds contributed to the self-healing ability of the PEP-PAM hydrogel, and the surface groups on the hydrogel allowed for tissue adhesiveness and natural antioxidant properties. Additionally, human epidermal growth factor-loaded PEP-PAM hydrogel promoted cell proliferation and migration in vitro and significantly accelerated wound healing in vivo on model rats. These progresses suggested a prospect for the PEP-PAM hydrogel as an effective and easily available wound dressing material. Remarkably, this work showcases that a wound dressing hydrogel can be facially developed by using natural polysaccharides as a one component and offers a new route for the high-value utilization of disastrous marine blooming biomass by transforming it into a biomedical material.

Novel asymmetric cyclodextrin derivatives have been synthesized. The materials form self‐assembled host monolayer thin films under the action of silane coupling reagents. Ultrasensitive (low‐ppm) sensors for volatile organic compounds have been developed based on these and related materials, and it is suggested that pattern recognition with an array of such sensors could be a feasible approach to the identification of a particular organic material.

A novel approach to covalently attached polymer films by surface functionalization and hydrosilylation reaction with reactive polymers on the surface is reported. Stable, uniform, and highly sensitive thin film sensors can thus be fabricated. The covalent attachment of polymer through a silane linker results in films with high uniformity, stability, and reasonable reproducibility as far as film thickness is concerned. Incorporation of molecular recognition reagents into the sensing film increases the sensor sensitivity dramatically, which is critical for detecting vapors such as certain explosives at parts per thousand or parts per billion levels. The sensors fabricated can detect o-nitrotoluene, a TNT simulant, at parts per billion concentrations.

There is evidence to show that downregulation of miR-1 expression is closely related to cancer progression, including in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms underlying miR-1 downregulation in NPC remain largely unknown, especially its association with Epstein-Barr virus (EBV). In this study we found that restoration of miR-1 dramatically inhibited cell invasion in vitro, together with tumour growth and metastasis in vivo. Importantly, we found that LMP1, an Epstein-Barr virus (EBV)-associated protein, suppressed miR-1 expression. Furthermore, we identified K-ras as a novel direct target of miR-1. Our results demonstrated for the first time that miR-1 was suppressed by LMP1 and its tumour-suppressive effects were mediated chiefly by repressing K-ras expression. We propose that miR-1 could serve as an independent biomarker to identify patients with different clinical characteristics.

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