Currently, there is no vaccine available that is able to cure cancer. The success of an antitumor vaccine will depend on its ability to induce robust and sustained tumor-specific immune responses. There is evidence to suggest that antitumor vaccination can induce such responses and even tumor regression. However, to date these regressions have not been long-lasting. Researchers at the Ludwig Institute for Cancer Research in Switzerland have developed a lentiviral vaccine which following injection into mice is capable of inducing an antigen-specific T cell response. This approach represents an attractive candidate for cancer therapy.
The crucial stimulation of a T cell response is dependent on the presentation of the antigen by host dendritic cells (DCs). As part of earlier strategies, the antigen of interest has been transferred to host DCs (by a process called “transduction”) outside the body and the DCs then reintroduced into the host. Unfortunately, this is a costly and labor-intensive process.
In the June 2 issue of the Journal of Clinical Investigation, Christopher Esslinger and colleagues describe their use of a third generation lentivector capable of transducing DCs in vivo in mice and inducing a very strong antigen-specific immune response. The immune response was shown to be superior to methods using DCs transduced outside the body in terms of both amplitude and persistence.
“Our results demonstrate that the time-consuming and costly steps currently used to elicit tumor-specific cytotoxic T lymphocyte responses through the transfer of ex-vivo manipulated DCs could be replaced by the much simpler direct in vivo administration of antigen recombinant lentivectors” states Dr. Esslinger.
TITLE: In vivo administration of a lentiviral vaccine targets DCs and induces efficient CD8+ T cell responses
AUTHOR CONTACT:
Christoph Esslinger
Ludwig Institute for Cancer Research, Epalinges, Switzerland.
Phone: 41-21-692-5985
Fax: 41-21-653-4474
Email: christoph.esslinger@isrec.unil.ch
View the PDF of this article at: https://www.the-jci.org/press/17098.pdf
Targeting the treatment of prostate cancer
Prostate cancer has the highest incidence of any malignancy and is the second cause of cancer-related deaths in men in industrialized countries. The male sex hormone androgen plays a key role in the spread of cancer from the prostate to the bones and lymph nodes. Drug-mediated androgen suppression is the current leading treatment, however as tumor cells progress they become androgen-independent and therefore insensitive to such therapy. A new study reveals the human prostate cancer cells express a specific type of receptor – a1-adrenergic receptors --– and drugs that block these receptors have great potential in the treatment of prostate cancer.
TITLE: a1-adrenergic receptors activate Ca2+-permeable cationic channels in prostate cancer epithelial cells
AUTHOR CONTACT:
Natalia Prevarskaya
Universite des Sciences et Technologies de Lille, Villeneuve d'Ascq Cedex, France.
Phone: 33-3-20-33-60-18
Fax: 33-3-20-43-40-66
E-mail: phycel@univ-lille1.fr
View the PDF of this article at: https://www.the-jci.org/press/16293.pdf
Newborn vaccination: Babies more prepared than previously thought
The increased susceptibility of newborns to infectious diseases is generally ascribed to developmentally related deficiencies in immune function. A new study demonstrates the presence in newborns of a mature and functional immune response to a cytomegalovirus infection and suggests that the machinery necessary to prime such responses is present in utero, thereby raising questions related to neonatal vaccination.
TITLE: Mature CD8+ T lymphocyte response to viral infection during fetal life
AUTHOR CONTACT:
Arnaud Marchant
Weatherall Institute of Molecular Medicine, Oxford, United Kingdom.
Phone: 44-1865-222-477
Fax: 44-1865-222-502
E-mail: arnaud.marchant@btinternet.com
View the PDF of this article at: https://www.the-jci.org/press/17470.pdf
ACCOMPANYING COMMENTARY:
Functionally mature virus-specific CD8+ T memory cells in congenitally infected newborns: proof of principle for neonatal vaccination?
AUTHOR CONTACT:
Patrick G. Holt
Telethon Institute for Child Health Research, West Perth, Western Australia, Australia.
Phone: 61-8-9489-7838
Fax: 618-9489-7707
E-mail: patrick@ichr.uwa.edu.au
View the PDF of this commentary at: https://www.the-jci.org/press/18805.pdf
Location, location, location: Tissue specificity of Chlamydia
The bacterium Chlamydia trachomatis is a primary cause of preventable blindness as well as urogenital infection. Research now demonstrates that the correlation between the preferred location – ocular versus genital – of this organism is linked to the presence or absence of a cluster of tryptophan synthesis genes. There may also exist unique host-parasite interactions in reaction to the host immune response that contribute to persistent chlamydial infection.
TITLE: Polymorphisms in Chlamydia trachomatis tryptophan synthase genes differentiate between genital and ocular isolates
AUTHOR CONTACT:
Grant McClarty
University of Manitoba, Winnipeg, Manitoba, Canada.
Phone: (204) 789-3307
Fax: (204) 789-3926
E-mail: mcclart@cc.umanitoba.ca
View the PDF of this article at: https://www.the-jci.org/press/17993.pdf
ACCOMPANYING COMMENTARY:
New insights into a persistent problem -- chlamydial infections
AUTHOR CONTACT:
Richard P. Morrison
Montana State University, Bozeman, Montana, USA.
Phone: (406) 994-7959
Fax: (406) 994-4926
E-mail: morrison@montana.edu
View the PDF of this commentary at: https://www.the-jci.org/press/18770.pdf
A jack of all trades: antimicrobial polypeptides
Antimicrobial peptides have been shown to possess microbicidal as well and pro- or anti-inflammatory activities. Their role is now widening following evidence that one such multifunctional peptide, LL-37, induces angiogenesis, a process essential for host defense, would healing, and tissue repair.
TITLE: An angiogenic role for the human peptide antibiotic LL-37/hCAP-18
AUTHOR CONTACT:
Robert Bals
Hospital of the University of Marburg, Marburg, Germany.
Phone: 49- 0-6421-2866451
Fax: 49-0-6421 2868987
Email: bals@mailer.uni-marburg.de
View the PDF of this article at: https://www.the-jci.org/press/17545.pdf
ACCOMPANYING COMMENTARY:
What is the real role of antimicrobial polypeptides that can mediate several other inflammatory responses?
AUTHOR CONTACT:
Peter Elsbach
New York University School of Medicine, New York, New York, USA.
Phone: (212) 263-5633
Fax: (212) 263-3952
Email: elsbap01@mcrcr.med.nyu.edu
View the PDF of this commentary at: https://www.the-jci.org/press/18761.pdf
In the thick of the thyroid
The maintenance of constant levels of thyroid hormones is essential for proper human development and growth. A study in mice has revealed the mechanism of thyroid hormone synthesis and release, which may aid further research and better our understanding of the molecular mechanisms that lead to human thyroid disorders such as hyperthyroidism.
TITLE: Thyroid functions of mouse cathepsins B, K, and L
AUTHOR CONTACT:
Klaudia Brix
School of Engineering And Science, International University Bremen, Bremen, Germany.
Phone: 49-421-3246
Fax: 49-421-3249
Email: k.brix@iu-bremen.de
View the PDF of this article at: https://www.the-jci.org/press/15990.pdf
Building bones
Bone formation is a complex process, regulated by growth factors that are expressed by bone cells, incorporated into the bone matrix and released in active form when bone resorbs. Researchers have now discovered how to accelerate bone formation by manipulating specific steps in this process. These results point to a potential molecular target for future drug discovery for agents that enhance the formation of bone in treatment of diseases like osteoporosis.
TITLE: Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro
AUTHOR CONTACT:
I. R. Garrett
OsteoScreen, Inc., San Antonio, Texas, USA.
Phone: (210) 614-0770
Fax: (210) 614-0797
E-mail: garrett@osteoscreen.com
View the PDF of this article at: https://www.the-jci.org/press/16198.pdf
How to make the heart grow
Growth of the heart in early postnatal development occurs as a result of the natural increase in the size of cardiac cells. A new study reveals that a1-adrenergic receptors that are expressed on cardiac cells and have been shown to mediate some alterations in normal heart function are also required for normal postnatal cardiac development.
TITLE: The a1A/C- and a1B-adrenergic receptors are required for physiological cardiac hypertrophy in the double-knockout mouse.
AUTHOR CONTACT:
Paul C. Simpson
San Francisco Veterans Affairs Medical Center, San Francisco, California, USA.
Phone: (415) 221-4810 x3200
Fax: (415) 750-6950
E-mail: pcs@itsa.ucsf.edu
View the PDF of this article at: https://www.the-jci.org/press/16100.pdf
Knocking out actinin in the kidney
Mutations in the gene ACTN4, which encodes a-actinin-4, cause scarring within the small blood vessels of the kidney where blood is filtered and waste products removed. Researchers have developed a mouse that lacks this gene, which will provide an important animal model for the further study of a-actinin-4–related kidney diseases.
TITLE: Mice deficient in a-actinin-4 have severe glomerular disease
AUTHOR CONTACT:
Martin Pollak
Brigham And Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Phone: (617) 525-5840
Fax: (617) 525-5841
E-mail: mpollak@rics.bwh.harvard.edu
View the PDF of this article at: https://www.the-jci.org/press/17988.pdf
How sex steroids protect against bone loss
TITLE: Kinase-mediated regulation of common transcription factors accounts for the bone-protective effects of sex steroids
AUTHOR CONTACT:
Stavros C. Manolagas
University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Phone: (501)-686-5130
Fax: (501)-686-8148
E-mail: manolagasstavros@uams.edu
View the PDF of this article at: https://www.the-jci.org/press/17261.pdf
ACCOMPANYING COMMENTARY:
A new hypothesis for how sex steroid hormones regulate bone mass
AUTHOR CONTACT:
Joseph Lorenzo
University of Connecticut Health Center, Farmington, Connecticut, USA.
Phone: (860) 679-8199
Fax: (860) 679-1040
E-mail: jlorenzo@nso2.uchc.edu
View the PDF of this commentary at: https://www.the-jci.org/press/18812.pdf
Channeling new treatments for multiple sclerosis
TITLE: The voltage-gated Kv1.3 K+ channel in effector memory T cells as new target for MS
AUTHOR CONTACT:
K. George Chandy
University of California at Irvine, Irvine, California, USA.
Phone: (949) 824-2133
Fax: (949)-824-3143
E-mail: gchandy@uci.edu
View the PDF of this article at: https://www.the-jci.org/press/16921.pdf
Key enzymes in tumor development
The secreted growth factor VEGF-C has been directly implicated in a number of human cancers. The regulation of VEGF-C conversion from its precursor, proVEGF-C, and the role of this conversion in tumor formation are unclear. Research now shows that proprotein convertases (PCs) are responsible for this processing, thus highlighting the potential use of PC-inhibitors to block the development of VEGF-C-induced malignancies.
TITLE: The secretory proprotein convertases furin, PC5, and PC7 activate VEGF-C to induce tumorigenesis
AUTHOR CONTACT:
Abdel-Majid Khatib
Ottawa Health Research Institute, Ottawa, Ontario, Canada.
Phone: (613) 798-5555 ext. 16086
Fax: (613) 761-4355
E-mail: mkhatib@ohri.ca
View the PDF of this article at: https://www.the-jci.org/press/17220.pdf
Enzyme deficiency produces skinny mice
TITLE: Obesity resistance and enhanced glucose metabolism in mice transplanted with white adipose tissue lacking acyl CoA:diacylglycerol acyltransferase 1
AUTHOR CONTACT:
Robert V. Farese Jr.
Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA.
Phone: 415-826-7500
Fax: 415-285-5632
E-mail: bfarese@gladstone.ucsf.edu
View the PDF of this article at: https://www.the-jci.org/press/15859.pdf
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