Engineered Cell-Based Therapeutics: Synthetic Biology Meets Immunology

Synthetic Biology has enabled new approaches to several medical applications including the development of immunotherapies based on bioengineered cells, and most notably the engineering of T-cells with tumor-targeting receptors, the Chimeric Antigen Receptor (CAR)-T cells. CAR-T-cells have successfully treated blood tumors such as large B-cell lymphoma and promise a new scenario of therapeutic interventions also for solid tumors. Learning the lesson from CAR-T cells, we can foster the reprogramming of T lymphocytes with enhanced survival and functional activity in depressing tumor microenvironment, or to challenge diseases such as infections, autoimmune and chronic inflammatory disorders. This review will focus on the most updated bioengineering approaches to increase control, and safety of T-cell activity and to immunomodulate the extracellular microenvironment to augment immune responses. We will also discuss on applications beyond cancer treatment with implications toward the understanding and cure of a broader range of diseases by means of mammalian cells engineering

Glatiramer Acetate (Copaxone) Modulates Platelet Activation and Inhibits Thrombin-Induced Calcium Influx: Possible Role of Copaxone in Targeting Platelets during Autoimmune Neuroinflammation

Background: Glatiramer acetate (GA, Copaxone, Copolymer-1) is an FDA approved drug for the treatment of MS and it is very effective in suppressing neuroinflammation in experimental autoimmune encephalitis (EAE), an animal model of MS. Although this drug was designed to inhibit pathogenic T cells, the exact mechanism of EAE/MS suppression by GA is still not well understood. Previously we presented evidence that platelets become activated and promote neuroinflammation in EAE, suggesting a possible pathogenic role of platelets in MS and EAE. We hypothesized that GA could inhibit neuroinflammation by affecting not only immune cells but also platelets. Methodology/Principal Findings We investigated the effect of GA on the activation of human platelets in vitro: calcium influx, platelet aggregation and expression of activation markers. Our results in human platelets were confirmed by in-vitro and in-vivo studies of modulation of functions of platelets in mouse model. We found that GA inhibited thrombin-induced calcium influx in human and mouse platelets. GA also decreased thrombin-induced CD31, CD62P, CD63, and active form of αIIbβ3 integrin surface expression and formation of platelet aggregates for both mouse and human platelets, and prolonged the bleeding time in mice by 2.7-fold. In addition, we found that GA decreased the extent of macrophage activation induced by co-culture of macrophages with platelets. Conclusions: GA inhibited the activation of platelets, which suggests a new mechanism of GA action in suppression of EAE/MS by targeting platelets and possibly preventing their interaction with immune cells such as macrophages. Furthermore, the reduction in platelet activation by GA may have additional cardiovascular benefits to prevent thrombosis

Cartoon 5: Integration - page 2 (in Russian)

This cartoon - the second of two - is about the wider promotion of an institutional research process in biological and chemical security education in the Higher Education sector

Cartoon 5: Integration - page 1 (in Russian)

This cartoon - the first of two - is about the wider promotion of an institutional research process in biological and chemical security education in the Higher Education sector

Cartoon folder cover - back page (in Russian)

This is the Russian version of the back cover page for a series of cartoons about the development and promotion of biological and chemical security education in the Higher Education sector

Cartoon 1: Preventing biological weapons - page 1 (2017) (in Russian)

This is the first cartoon (of 2) within project "Informing Policymakers of the Progress in Strengthening the Chemical and Biological Weapons Non-Proliferation Regime"

Cartoon 3: Education and awareness-raising - page 1 (in Russian)

This cartoon - the first of two - is about the development of biological and chemical security education and awareness-raising in the Higher Education sector

Cartoon folder cover - front page (in Russian)

This is the Armenian version of the front cover for a series of cartoons about the development and promotion of biological and chemical security education in the Higher Education sector

Cartoon 4: Evaluation - page 2 (in Russian)

This cartoon - the second of two - is about the development of an institutional research process in biological and chemical security education in the Higher Education sector

Cartoon 1: Preventing biological weapons - page 2 (2021) (in Russian)

This is the second cartoon (of 2) within project on "Informing Policymakers of the Progress in Strengthening the Chemical and Biological Weapons Non-Proliferation Regime"