A three-in-one approach to cancer vaccines

Summaries of newsworthy papers include Neurodegeneration: Prion structure unfolds, New drug to treat schizophrenia, Adult stem cell with muscle, The genetics of human height, Stop that itch!, Restraining allergic responses


For papers that will be published online on 02 September 2007

This press release contains:

· Summaries of newsworthy papers:

Neurodegeneration: Prion structure unfolds – Nature

A three-in-one approach to cancer vaccines – Nature Chemical Biology

New drug to treat schizophrenia – Nature Medicine

Adult stem cell with muscle – Nature Biotechnology

The genetics of human height – Nature Genetics

Stop that itch! – Nature Immunology

Restraining allergic responses – Nature Immunology

· Mention of papers to be published at the same time with the same embargo

· Geographical listing of authors

PDFs of all the papers mentioned on this release can be found in the relevant journal’s section of http://press.nature.com. Press contacts for the Nature journals are listed at the end of this release.

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NOTE: Once a paper is published, the digital object identifier (DOI) number can be used to retrieve the abstract and full text from the journal web site (abstracts are available to everyone, full text is available only to subscribers). To do this, add the DOI to the following URL: http://dx.doi.org/ (For example, http://dx.doi.org/10.1038/ng730). For more information about DOIs and Advance Online Publication, see http://www.nature.com/ng/aop/.




[1] Neurodegeneration: Prion structure unfolds

DOI: 10.1038/nature06108

Researchers have probed the structure of the yeast prion protein Sup35, and discovered how structural changes between different prion strains can influence their infectivity and change the phenotypes they cause.

Prions, infectious proteins that cause a variety of diseases in different animals, occur as different strains. Online in this week’s Nature, Jonathan S. Weissman and colleagues present a comprehensive structural analysis of the complete, unmodified yeast Sup35 prion protein in two distinct infectious conformations. Both have an overlapping core of amyloid protein, comprising a glutamine/asparagine-rich first 40 residues. But in the weakest strain the structure is extended to 70 amino acids, explaining its higher stability and weaker propagating potential.

The team have succeeded where others have struggled. Previous structural studies had to make compromises, such as the use of small peptides or bulky modifying groups, to overcome technical challenges associated with the structural analyses of protein aggregates.

Author contact:

Jonathan S. Weissman (University of California, San Francisco, CA, USA)
Tel: +1 415 502 7642; E-mail: [email protected]

*************************************NATURE CHEMICAL BIOLOGY ***********************************


[2] A three-in-one approach to cancer vaccines

DOI: 10.1038/nchembio.2007.25

A single chemical structure that incorporates three vaccine components could prove powerful in treating cancer, according to a paper in the October issue of Nature Chemical Biology. Sugars are often highly expressed on the outside of cancer cells, and eliciting an immune response to these sugars could be an important vaccine strategy.

Previous attempts to develop anticancer vaccines against these overexpressed sugars have involved ‘two-component’ vaccines, which combine molecules that can induce antibody production by two different routes into a single chemical entity. However, these vaccines require very high levels of adjuvants—additional chemicals that are used to boost the immune response being elicited by the vaccine.

Geert-Jan Boons and colleagues have now developed a ‘three-component’ vaccine that chemically links the adjuvant to two other vaccine components. Chemically connecting these three vaccine pieces proved to be exceptionally powerful in inducing an immune response in mice. This vaccine strategy can now be tested for its ability to combat cancer, and the three-component approach could be applied to other vaccine targets.

Author contact:

Geert-Jan Boons (University of Georgia, Athens, GA, USA)

Tel: +1 706 542 9161; E-mail: [email protected]

*******************************************Nature MEDICINE********************************************


[3] New drug to treat schizophrenia

DOI: 10.1038/nm1632

A clinical trial in the September issue of Nature Medicine describes a drug that works effectively in people with schizophrenia by targeting glutamate-mediated neurotransmission.

Altered glutamate-mediated neurotransmission has repeatedly been linked to schizophrenia, but compelling evidence for its involvement has been lacking, and all commonly prescribed antipsychotic drugs act on dopamine receptors. Sandeep Patil and colleagues now report that a selective agonist of a specific subtype of glutamate receptors known as mGlu2/3 has antipsychotic effects in patients with the disease.

They evaluated their drug—LY2140023—in a double-blind, placebo-controlled trial in patients with schizophrenia, and compared how well it worked versus olanzapine, a commonly used antipsychotic compound that targets dopamine receptors. The authors found that patients treated with LY2140023 showed improvements in both positive (hallucinations, delusions and thought disorder) and negative (social withdrawal, apathy and emotional blunting) symptoms of schizophrenia compared to placebo after four weeks of treatment.

The results from this study indicate that mGlu2/3 receptor agonists have antipsychotic properties and represent the first credible alternative treatment for schizophrenia that does not target dopamine.

Author contacts:

Sandeep Patil (Takeda Global Research & Development Center, Deerfield, IL, USA)Development Tel: +1 224 554 5403; E-mail: [email protected]

James Monn (Eli Lilly and Company, Indianapolis, IN, USA)

Tel: +1 317 276 9101; E-mail: [email protected]

Other papers from Nature Medicine to be published online at the same time and with the same embargo:

[4] Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock

DOI: 10.1038/nm1638

[5] Death-receptor O-glycosylation controls tumor cell sensitivity to the proapoptotic ligand Apo2L/TRAIL

DOI: 10.1038/nm1627

*******************************************NATURE BIOTECHNOLOGY*********************************


[6] Adult stem cell with muscle

DOI: 10.1038/nbt1334

A ready source of muscle progenitor cells might be useful for treating diseases that involve muscle atrophy, such as muscular dystrophy. In a paper to be published online this week in Nature Biotechnology, Johnny Huard and colleagues describe a type of cell in human adult skeletal muscle with a greater capacity to regenerate muscle tissue than progenitor cells (or ‘satellite cells’) previously isolated from muscles.

The new progenitors, called myoendothelial cells, express cell-surface markers of both satellite cells and endothelial (blood vessel) cells. They are easily isolated using fluorescently labelled antibodies against the markers and a fluorescence-activated cell sorting machine. They can be differentiated in culture dishes towards muscle, bone and cartilage. Studies in mice indicate that myoendothelial cells are much more efficient at forming muscle fibres in the body than both satellite and endothelial cells: 1000 myoendothelial cells transplanted into the injured skeletal muscle of immunodeficient animals produce on average 89 muscle fibres, whereas the same number of endothelial or satellite cells generate only 9 and 5 muscle fibres, respectively. Tests to investigate the safety of myoendothelial cells suggest that they have no propensity to form tumours.

Author contact:

Johnny Huard (University of Pittsburgh, PA, USA)
Tel: +1 412 692 7807; E-mail: [email protected]

***********************************************NATURE GENETICS **************************************


[7] The genetics of human height

DOI: 10.1038/ng2121

A variant in a gene called HMGA2 is associated with differences in adult and childhood height in the general population, reports a study to be published online this week in Nature Genetics. This is the first such common variant to be reproducibly associated with human stature, and likely heralds a new wave of studies associating genetic variation with non–disease-related complex traits in humans.

Studies of twins have shown that up to 90% of the normal variation in human height is due to genetic variation, with such variants likely to be distributed among a large number of genes. A large consortium of investigators led by Timothy Frayling, Joel Hirschhorn, and Mark McCarthy carried out a genome-wide association study of nearly 5,000 individuals, and found two variants very close to HMGA2 to be associated with variation in height. A follow-up study of more then 19,000 individuals confirmed the association.

HMGA2 is an excellent candidate to be associated with height, as rare, severe mutations in the gene cause dramatic alterations of body size in mice and humans. Although the effect of these common HMGA2 variants is small—explaining approximately 0.3% of population variation in height, or approximately 0.4 cm increased height per copy in an individual—the success of the study suggests that additional genes will soon be associated with height and other visible traits in humans.

Author contact:

Timothy Frayling (Peninsula Medical School, Exeter, UK)

Tel: +44 1392 262 935; E-mail: [email protected]

Other papers from Nature Genetics to be published online at the same time and with the same embargo

[8] A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15

DOI: 10.1038/ng2108

[9] Modulation of morphogenesis by noncanonical Wnt signaling requires ATF/CREB family–mediated transcriptional activation of TGFβ2

DOI: 10.1038/ng2112

[10] Variation in complement factor 3 is associated with risk of age-related macular degeneration

DOI: 10.1038/ng2131

*******************************************NATURE IMMUNOLOGY ************************************


[11] Stop that itch!

DOI: 10.1038/ni1503

Immune cells in the skin secrete a chemical that limits the inflammatory response to poison ivy and sunburn, according to a report online in this week’s Nature Immunology.

Stephen Galli and colleagues look at how the immune system responds to irritants such poison ivy and poison oak or to sunburn, all of which can lead to blistering of the skin. Their research identifies mast cells, a form of immune cell that resides in the skin, as the source of interleukin 10 (IL-10), a molecule known to suppress immune responses. Mice that lack mast cells or have mutant mast cells that are unable to make IL-10 develop larger skin lesions, which last much longer, than those of normal mice upon exposure to the irritant found in poisonous plants. The mutant mice also display higher numbers of T cells recruited to the affected skin lesions.

The work identifies a new role for mast cells, which have been previously associated with releasing mediators of allergic reactions. The authors utilize these findings to manipulate mast cell release of IL-10 in settings of skin inflammation and irritation to limit further damage. These findings might lead to new therapies for skin damage.

Author contact:

Stephen Galli (Stanford University School of Medicine, Stanford, CA, USA)

Tel: +1 650 723 7975; E-mail: [email protected]

[12] Restraining allergic responses

DOI: 10.1038/ni1506

A cellular process crucial for preventing allergy is presented in a paper published online this week in Nature Immunology.

Certain varieties of immune cells release interleukin 4, a protein that, upon binding to its receptor, triggers signals that promote hallmark features of allergy. Yoshinori Fukui and colleagues show that interleukin 4 receptors expressed on the surface of immune cells called T cells are quickly internalized, directed along the complex network of protein ‘fibres’ that support T cell structure and shape, and ultimately routed into cellular compartments for degradation. This ‘harness’ on interleukin 4 expression is interrupted in T cells lacking Dock2, a protein responsible for regulating the ‘trafficking’ of internalized cargo. As a result Dock2-deficient T cells display excessive amounts of interleukin-4 receptors and Dock2-deficient mice suffer from spontaneous allergic inflammation. Whether Dock2 regulates the intracellular fate of other T cell surface proteins remains for future investigations.

Author contact:

Yoshinori Fukui (Kyushu University, Fukuoka, Japan)

Tel: +81 92 642 6828; E-mail: [email protected]

Other papers from Nature Immunology to be published online at the same time and with the same embargo:

[13] Minimal activation of memory CD8+ T cells by tissue-derived dendritic cells favors the activation of naïve CD8+ T cells

DOI: 10.1038/ni1505


Items from other Nature journals to be published online at the same time and with the same embargo:

Nature PHYSICS (http://www.nature.com/naturephysics)

[14] Experiments and multiscale simulations of laser propagation through ignition-scale plasmas

DOI: 10.1038/nphys709

[15] Focusing capillary jets close to the continuum limit

DOI: 10.1038/nphys710

NATURE MATERIALS (http://www.nature.com/naturematerials)

[16] Dynamic control of the Q factor in a photonic crystal nanocavity

DOI: 10.1038/nmat1994

NATURE NANOTECHNOLOGY (http://www.nature.com/nnano)

[17] Reversible fluorescence quenching in carbon nanotubes for biomolecular sensing

DOI: 10.1038/nnano.2007.261

[18] Nanoparticle printing with single-particle resolution

DOI: 10.1038/nnano.2007.262

[19] Synergetic nanowire growth

DOI: 10.1038/nnano.2007.263

[20] Self-formation of sub-60-nm half-pitch gratings with large areas through fracturing

DOI: 10.1038/nnano.2007.264 (N&V)

Nature NEUROSCIENCE (http://www.nature.com/natureneuroscience)

[21] A unique sorting nexin regulates trafficking of potassium channels via a PDZ domain interaction
DOI: 10.1038/nn1953

[22] Forward and reverse hippocampal place-cell sequences during ripples
DOI: 10.1038/nn1961

[23] Nociceptive sensory neurons derive from contralaterally migrating, fate-restricted neural crest cells
DOI: 10.1038/nn1962

[24] Reestablishment of damaged adult motor pathways by grafted embryonic cortical neurons
DOI: 10.1038/nn1970

NATURE METHODS (http://www.nature.com/nmeth)

[25] Engineering tumors with 3D scaffolds

DOI: 10.1038/nmeth1085


***FOR IMMEDIATE RELEASE: The following paper was published on Nature Biotechnology’s website on Monday 27 August at 1000 London time (BST) / 1500 US Eastern time, so is no longer under embargo. The rest of this week’s press release remains under embargo until Sunday 02 September 1800 London time (BST) / 1300 US Eastern time.***

[26] Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells

DOI: 10.1038/nbt1335



The following list of places refers to the whereabouts of authors on the papers numbered in this release. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.

Melbourne: 13

Vienna: 3

Leuven: 9


Vedbaek: 21


Helsinki: 7


Bordeaux: 24

Evry: 8

Marcoussis: 18

Poitiers: 24


Munster: 4


Fukuoka: 12

Kyoto: 16

Saga: 12

Tokyo: 12


Amsterdam: 4

Eindhoven: 19


Khotkovo: 3

Moscow: 3

Nikolskoe: 3

St Petersburg: 3


Singapore: 3


Seville: 15


Malmo: 7

Stockholm: 9


Ruschlikon: 18

Zurich: 18


Bristol: 7

Dundee: 7

Exeter: 7

London: 8, 10

Oxford: 7, 8

Windlesham: 3



Irvine: 8

La Jolla: 9, 21

Livermore: 14

Los Angeles: 9, 14

Pasadena: 23

San Diego: 9

San Francisco: 1, 5

Stanford: 11


Athens: 2


Deerfield: 3


Indianapolis: 3, 5


Boston: 7, 10, 25

Cambridge: 7, 9, 10, 25, 26


Ann Arbor: 25


Bozeman: 23

New Jersey

Newark: 22

Princeton: 20

New Mexico

Los Alamos: 17

New York

Ithaca: 25


North Wales: 3

Pittsburgh: 6


Houston: 9


For media inquiries relating to embargo policy for all the Nature Research Journals:

Katherine Anderson (Nature London)

Tel: +44 20 7843 4502; E-mail: [email protected]

Ruth Francis (Senior Press Officer, Nature, London)

Tel: +44 20 7843 4562; E-mail: [email protected]

For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:

Nature Biotechnology (New York)

Peter Hare

Tel: +1 212 726 9284; E-mail: [email protected]

Nature Chemical Biology (Boston)

Andrea Garvey

Tel: +1 617 475 9241, E-mail: [email protected]

Nature Genetics (New York)

Orli Bahcall

Tel: +1 212 726 9311; E-mail: [email protected]

Nature Immunology (New York)

Laurie Dempsey

Tel: +1 212 726 9372; E-mail: [email protected]

Nature Materials (London)

Fabio Pulizzi

Tel: +44 20 7014 4024; E-mail: [email protected]

Nature Medicine (New York)

Juan Carlos Lopez

Tel: +1 212 726 9325; E-mail: [email protected]

Nature Methods (New York)

Allison Doerr

Tel: +1 212 726 9393; E-mail: [email protected]

Nature Nanotechnology (London)

Peter Rodgers

Tel: +44 20 7014 4019; Email: [email protected]

Nature Neuroscience (New York)

Sandra Aamodt (based in California)

Tel: +1 530 795 3256; E-mail: [email protected]

Nature Physics (London)

Alison Wright

Tel: +44 20 7843 4555; E-mail: [email protected]

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