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March 08, 2011

Cholesterol link to immune system and a molecular switch can turn on cancer vaccines

1. A study by Edinburgh University scientists found when the body succumbs to a viral infection a hormone in the immune system lowers cholesterol. It may be possible to use cholesterol lowering drugs to also boost the immune system. A new treatment could help overcome the problems associated with antibiotic resistance, as it enhances the way the body responds to an infection, instead of focusing on attacking the infection itself.



2. The immune system is capable of recognizing tumor growth, and naturally mounts an anti-cancer defense. Dendritic cells (DCs) can take up tumor-derived molecules (antigens) and present them to T cells, and those "primed" T cells are then able to recognize and kill tumor cells.

A combination of methods improved DC-mediated tumor antigen-specific T cell responses in mouse cancer models and T cell responses to human tumor antigens. The researchers hope that this "switch" might be broadly applicable to the design of DC vaccines.

Journal of Clinical Investigation - A composite MyD88/CD40 switch synergistically activates mouse and human dendritic cells for enhanced antitumor efficacy

The in vivo therapeutic efficacy of DC-based cancer vaccines is limited by suboptimal DC maturation protocols. Although delivery of TLR adjuvants systemically boosts DC-based cancer vaccine efficacy, it could also increase toxicity. Here, we have engineered a drug-inducible, composite activation receptor for DCs (referred to herein as DC-CAR) comprising the TLR adaptor MyD88, the CD40 cytoplasmic region, and 2 ligand-binding FKBP12 domains. Administration of a lipid-permeant dimerizing ligand (AP1903) induced oligomerization and activation of this fusion protein, which we termed iMyD88/CD40. AP1903 administration to vaccinated mice enabled prolonged and targeted activation of iMyD88/CD40-modified DCs. Compared with conventionally matured DCs, AP1903-activated iMyD88/CD40-DCs had increased activation of proinflammatory MAPKs. AP1903-activated iMyD88/CD40-transduced human or mouse DCs also produced higher levels of Th1 cytokines, showed improved migration in vivo, and enhanced both antigen-specific CD8+ T cell responses and innate NK cell responses. Furthermore, treatment with AP1903 in vaccinated mice led to robust antitumor immunity against preestablished E.G7-OVA lymphomas and aggressive B16.F10 tumors. Thus, the iMyD88/CD40 unified “switch” effectively and safely replaced exogenous adjuvant cocktails, allowing remote and sustained DC activation in vivo. DC “licensing” through iMyD88/CD40 may represent a mechanism by which to exploit the natural synergy between the TLR and CD40 signaling pathways in DCs using a single small molecule drug and could augment the efficacy of antitumor DC-based vaccines.

3. King's College London - an advanced computer program can accurately detect the early signs of Alzheimer's disease from a routine clinical brain scan. The new scan can return 85 per cent accurate diagnostic results in under 24 hours.

The 'Automated MRI' software automatically compares or benchmarks someone’s brain scan image against 1200 others, each showing varying stages of Alzheimer’s disease. This collection of images is thought to be the largest of its kind in the world.

Normally in routine clinical practice, brain scans are used to simply exclude diseases that can mimic Alzheimer’s disease, but here automated MRI software is being used for the first time in a NHS setting (Memory Clinics) to make an early and accurate diagnosis of the illness.

Early diagnosis of Alzheimer's is clinically difficult and patients with the early signs are frequently not treated until their symptoms become stronger.

An early diagnosis allows someone to plan their care before the condition worsens - helping to prevent institutionalisation, dramatically improving their quality of life. It is also a cost effective and efficient way to manage and organise treatment of the disease.

There are 750,000 people with dementia in the UK. The financial cost of dementia to the UK is over £20 billion a year. According to the Alzheimer’s Society, in just 15 years a million people will be living with dementia. This will soar to 1.7 million people (in the UK alone) by 2051.

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