Argos Therapeutics Publishes Novel Approach to Improving Stimulation of Immunotherapeutic Pathways Via Dendritic Cells
Argos Therapeutics today announced the publication of an article in the online journal BMC Molecular Biology 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 of RNA 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 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, 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 transfection 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) dendritic cells to trigger a pathogen- or tumor-specific immune response. 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