Identification of human progenitors of exhausted CD8 T cells associated with elevated IFN-γ response in early phase of viral infection.

T cell exhaustion is a hallmark of hepatitis C virus (HCV) infection and limits protective immunity in chronic viral infections and cancer. Limited knowledge exists of the initial viral and immune dynamics that characterise exhaustion in humans. We studied longitudinal blood samples from a unique cohort of individuals with primary infection using single-cell multi-omics to identify the functions and phenotypes of HCV-specific CD8 T cells.

Haematopoietic Stem Cell Transplantation Results in Extensive Remodelling of the Clonal T Cell Repertoire in Multiple Sclerosis.

Autologous haematopoietic stem cell transplantation (AHSCT) is a vital therapeutic option for patients with highly active multiple sclerosis (MS). Rates of remission suggest AHSCT is the most effective form of immunotherapy in controlling the disease. Despite an evolving understanding of the biology of immune reconstitution following AHSCT, the mechanism by which AHSCT enables sustained disease remission beyond the period of lymphopenia remains to be elucidated.

Prophylactic antigen-specific T-cells targeting seven viral and fungal pathogens after allogeneic haemopoietic stem cell transplant.

Objectives: Adoptive immunotherapy using donor-derived antigen-specific T-cells can prevent and treat infection after allogeneic haemopoietic stem cell transplant (HSCT).

Methods: We treated 11 patients with a prophylactic infusion of 2 × 10 cells per square metre donor-derived T-cells targeting seven infections (six viral and one fungal) following HSCT. Targeted pathogens were cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus, varicella zoster virus, influenza, BK virus (BKV) and .

enrichment of PRAME antigen-specific T cells for adoptive immunotherapy using CD137 activation marker selection.

Objective: Adoptive immunotherapy with expanded tumor-specific T cells has potential as anticancer therapy. Preferentially expressed antigen in melanoma (PRAME) is an attractive target overexpressed in several cancers including melanoma and acute myeloid leukaemia (AML), with low expression in normal tissue outside the gonads. We developed a GMP-compliant manufacturing method for PRAME-specific T cells from healthy donors for adoptive immunotherapy.

Rapidly expanded partially HLA DRB1-matched fungus-specific T cells mediate in vitro and in vivo antifungal activity.

Invasive fungal infections are a major cause of disease and death in immunocompromised hosts, including patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). Recovery of adaptive immunity after HSCT correlates strongly with recovery from fungal infection. Using initial selection of lymphocytes expressing the activation marker CD137 after fungal stimulation, we rapidly expanded a population of mainly CD4+ T cells with potent antifungal characteristics, including production of tumor necrosis factor α, interferon γ, interleukin-17, and granulocyte-macrophage colony stimulating factor.

Could cannabis liberalisation lead to wider changes in drug policies and outcomes?

Cannabis policies are changing in some countries. This may have consequences that extend beyond cannabis-specific outcomes, such as an impact on the consumption patterns of other substances. Changes in cannabis policies may also influence policy responses to other drugs, as countries re-assess the balance between law enforcement and public health objectives.

Controlling new drugs under marketing regulations.

Aims: The rapid emergence of myriad substances openly marketed as 'legal highs' is straining traditional drug control systems which require time and basic scientific data on harms to react, presenting governments with the dilemma of no response or a disproportionate response. Some countries have side-stepped this using novel policy and legislative approaches. Should other countries consider them?

Methods: We review the different laws invoked to stop the open sale of new psychoactive substances, focusing on the European Union (EU).

Khat use and monitoring drug use in Europe: the current situation and issues for the future.

Aim Of The Study: To review the information available on the use of khat (Catha edulis) in the EU, and to assess the future use of this drug and related substances.

Material And Methods: Khat is not controlled by international law and it has not been systematically included in the list of illicit drugs monitored in the EU. The current principal source of information on khat use in Europe is the early-warning system set up to monitor new and emerging drugs.

New for old? Risperidone long-acting injection in older patients.

Objective: To describe six older patients who were treated with risperidone long-acting injection, and to discuss the role of this medication in a psychogeriatric setting.

Method: Case series.

Results: Of the six patients trialled on risperidone long-acting injection, two remain on this treatment.