Genetically engineered T cells expressing a chimeric antigen receptor (CAR) are rapidly emerging a promising new treatment for haematological and non-haematological malignancies. CAR-T therapy can induce rapid and durable clinical responses but is associated with unique acute toxicities. Moreover, CAR-T cells are vulnerable to immunosuppressive mechanisms. Here, we report that CAR-T cells release extracellular vesicles, mostly in the form of exosomes that carry CAR on their surface. The CAR-containing exosomes express a high level of cytotoxic molecules and inhibit tumour growth. Compared with CAR-T cells, CAR exosomes do not express Programmed cell Death protein 1 (PD1), and their antitumour effect cannot be weakened by recombinant PD-L1 treatment. In a preclinical in vivo model of cytokine release syndrome, the administration of CAR exosomes is relatively safe compared with CAR-T therapy. This study supports the use of exosomes as biomimetic nanovesicles that may be useful in future therapeutic approaches against tumours.
Antibodies are considered as an excellent foundation to neutralize pathogens and as highly specific therapeutic agents. Antibodies are generated in response to a vaccine but little use as immunotherapy to combat virus infections. A new generation of broadly cross-reactive and highly potent antibodies has led to a unique chance for them to be used as a medical intervention. Neutralizing antibodies (monoclonal and polyclonal antibodies) are desirable for pharmaceutical products because of their ability to target specific epitopes with their variable domains by precise neutralization mechanisms. The isolation of neutralizing antiviral antibodies has been achieved by Phage displayed antibody libraries, transgenic mice, B cell approaches, and hybridoma technology. Antibody engineering technologies have led to efficacy improvements, to further boost antibody in vivo activities. “Although neutralizing antiviral antibodies have some limitations that hinder their full development as therapeutic agents, the potential for prevention and treatment of infections, including a range of viruses (HIV, Ebola, MERS-COV, CHIKV, SARS-CoV, and SARS-CoV2), are being actively pursued in human clinical trials.”
Carnivorous fish is thought to be high-glucose intolerance. But the reasons were still unclear. The aim of the present study is to investigate the effects of high level of dietary carbohydrate on the survival, growth and immune responses of Paralichthys olivaceus, and the underlying molecular mechanism related to the immune and glucose metabolism. P. olivaceus were fed with 8%, 16% and 24% of dietary carbohydrate for 10 weeks, respectively. After that, a glucose tolerance test (GTT) was conducted. Results showed that excessive (24%) dietary carbohydrate significantly decreased the growth and glucose tolerance ability according to the GTT. It significantly increased hepatic NADPH oxidase activity and malondialdehyde content and serum contents of IL-6 and advanced glycation end products. The expressions of glucose transport-relevant genes in liver and the content of related hormones in serum were analyzed. In conclusion, it was confirmed that IL-6 increased the expression of suppressor of cytokine signaling 3 (SOCS3) and regulated the downstream targets of PI3K-AKT mediated signal transduction, and then downregulated the glucose transporter 2 activity in liver of P. olivaceus fed diet with excessive carbohydrate level. It was suggested that SOCS3 served as a bridge between immune response and glucose metabolism in P. olivaceus.
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