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Argos Therapeutics Publishes Novel Approach to Improving Stimulation of Immunotherapeutic Pathways via Dendritic Cells.


DURHAM, N.C. -- Argos Therapeutics today announced the publication of an article in the online journal BMC (BMC Software, Inc., Houston, TX, www.bmc.com) A leading supplier of software that supports and improves the availability, performance, and recovery of applications in complex computing environments.  Molecular Biology molecular biology, scientific study of the molecular basis of life processes, including cellular respiration, excretion, and reproduction. The term molecular biology was coined in 1938 by Warren Weaver, then director of the natural sciences program at the Rockefeller  supporting the Company's novel method of stimulating the CD40 receptor signal cascade in dendritic cells (DCs), which may potentially improve the potency of their DC-based immunotherapy. Argos' process involves electroporation electroporation (i·lekˈ·trō·p·rāˑ·sh  of RNA RNA: see nucleic acid.
RNA
 in full ribonucleic acid

One of the two main types of nucleic acid (the other being DNA), which functions in cellular protein synthesis in all living cells and replaces DNA as the carrier of genetic
 into DCs, encoding a modified version of the T-cell protein CD40L. Stimulating this receptor signal cascade through ectopic expression of this novel CD40L RNA results in secretion of the downstream inflammatory cytokine Cytokine

Any of a group of soluble proteins that are released by a cell to send messages which are delivered to the same cell (autocrine), an adjacent cell (paracrine), or a distant cell (endocrine).
 IL-12 from the electroporated DCs. This new approach is part of the Company's Arcelis[TM] technology, a proprietary platform for creating personalized immunotherapies for HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. , other infectious diseases, and cancer.

The study demonstrates improved activation of the CD40 receptor signal cascade by CD40L-encoding RNA modified via post-transcriptional capping of the RNA combined with site-directed mutagenesis to optimize the length of the RNA-encoded protein. These modifications were shown to generate an approximately one-log increase in IL-12 levels by the transfected DC, indicating improved stimulation of the target immunotherapeutic pathway.

"This study validates Argos' optimized method for synthesizing RNA and may support an enhanced level of immunopotency," said Charles Nicolette, Ph.D, Chief Scientific Officer of Argos. "We believe that this is the first report describing improved protein expression of post-transcriptionally capped RNA in dendritic cells. Importantly, Argos has shown that this finding may have broad utility for optimizing protein expression from RNA in DCs and other cells. While it was previously understood that DNA DNA: see nucleic acid.
DNA
 or deoxyribonucleic acid

One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes.
 transfection trans·fec·tion
n.
Infection of a bacterium or cell with DNA or RNA isolated from a bacteriophage or from an animal or a plant virus, resulting in replication of the complete virus.
 of CD40L can generate CD40 receptor signal cascade activation, Argos has now demonstrated that a similar, even enhanced effect can be achieved through RNA electroporation."

The article, titled "Ectopic expression of post transcriptionally capped RNA encoding for truncated CD40L in DCs induces high level of IL-12 secretion," was authored by Irina Tcherepanova, Melissa Adams, Xiaorong Feng, Atsushi Hinohara, Joe Horvatinovich, David Calderhead, Don Healey and Charles A. Nicolette and can be found in the October 17, 2008 edition of BMC Molecular Biology.

About the Arcelis[TM] Technology

Arcelis is Argos' proprietary technology for personalizing RNA-loaded dendritic cell immunotherapies for HIV, other infectious diseases, and cancer. This platform is based on optimizing a patient's own (autologous autologous /au·tol·o·gous/ (aw-tol´ah-gus) related to self; belonging to the same organism.

au·tol·o·gous
adj.
1.
) dendritic cells to trigger a pathogen- or tumor-specific immune response immune response
n.
An integrated bodily response to an antigen, especially one mediated by lymphocytes and involving recognition of antigens by specific antibodies or previously sensitized lymphocytes.
. To address the challenge of the unique genetic profile of each patient's disease and the genetic mutations of that disease, Argos loads the autologous dendritic cells with a sample of messenger RNA ("mRNA") isolated from their disease. Through this process, dendritic cells can potentially prime immune responses to the entire antigenic repertoire, resulting in an immunotherapeutic that is customized to the patient's specific disease. The development of Arcelis is part of Argos' broad collaboration with Kyowa Hakko Kirin Co., Ltd.

About Argos Therapeutics, Inc.

Argos is an immunotherapy company developing new treatments for cancer, infectious and autoimmune diseases, and transplantation rejection. The Company has generated multiple platform technologies and a diverse pipeline of products based on its expertise in the biology of dendritic cells -- the master switch that turns the immune system on or off. www.argostherapeutics.com
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Publication:Business Wire
Date:Oct 28, 2008
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