— Early sign of Alzheimer's reversed in lab — One of the earliest known impairments caused by Alzheimer's disease - loss of sense of smell - can be restored by removing a plaque-forming protein in a mouse model of the disease,…
— Parental controls on embryonic development? — When a sperm fertilises an egg, each contributes a set of chromosomes to the resulting embryo, which at these very early stages is called a zygote. Early on, zygotic genes are inert,…
— Newly discovered heart stem cells make muscle and bone — Researchers have identified a new and relatively abundant pool of stem cells in the heart. The findings in the December issue of Cell Stem Cell, a Cell Press publication, show that…
— BUSM researchers develop blood test to detect membranous nephropathy — Research conducted by a pair of physicians at Boston University School of Medicine (BUSM) and Boston Medical Centre (BMC) has led to the development of a test that can help diagnose…
— New hip implants no better than traditional implants — New hip implants appear to have no advantage over traditional implants, suggests a review of the evidence published on bmj.com today…
— Action needed to improve men's health in Europe — Policies aimed specifically at men are urgently needed to improve the health of Europe's men, say experts on bmj.com today…
— Probiotics reduce infections for patients in intensive care — Traumatic brain injury is associated with a profound suppression of the patient's ability to fight infection. At the same time the patient also often suffers hyper-inflammation, due…
— High blood sugar levels in older women linked to colorectal cancer — Elevated blood sugar levels are associated with an increased risk of colorectal cancer, according to a study led by researchers at Albert Einstein College of Medicine of Yeshiva University.…
— Engineered botulism toxins could have broader role in medicine — The most poisonous substance on Earth - already used medically in small doses to treat certain nerve disorders and facial wrinkles - could be re-engineered for an expanded role in helping…
Using a molecular switch to turn on cancer vaccines
The immune system is capable of recognising tumour growth, and naturally mounts an anti-cancer defence. Dendritic cells (DCs) can take up tumour-derived molecules (antigens) and present them to T cells, and those 'primed' T cells are then able to recognise and kill tumour cells. In recent years, researchers have attempted to capitalise upon these natural immune responses to develop new therapies- namely, by generating a pool of tumour antigen-pulsed DCs that might be used as vaccines to augment the T-cell responses of cancer patients. In clinical trials, these DC vaccines have had limited success, in part because the protocols to generate mature and active DCs in vitro are imperfect. Specifically, generation of mature DCs requires activation of Toll-Like receptors (TLRs), usually achieved by administration of lipopolysaccharide, which can cause toxic shock in humans and can promote apoptosis.
In this paper, David Spencer and colleagues, of Baylor University in Houston, Texas, addressed this problem by looking to the adaptor molecule downstream of the TLR, MyD88. They engineered a form of MyD88 that could induce downstream signalling in response to a drug, and expressed this inducible MyD88 (iMyD88) in DCs. Further, the researchers combined iMyD88 with a second pathway required for optimal activation of DCs- CD40 signalling- so that they could control both pathways with administration of a single drug. This combination improved DC-mediated tumour antigen-specific T cell responses in mouse cancer models and T cell responses to human tumour antigens. The researchers hope that this 'switch' might be broadly applicable to the design of DC vaccines.
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