Argos Therapeutics Publishes Approach To Generating High-Avidity Cytotoxic T Cells With Dendritic Cell-Based Immunotherapy

Main Category: Clinical Trials / Drug Trials
Also Included In: Cancer / Oncology;  Infectious Diseases / Bacteria / Viruses;  Biology / Biochemistry
Article Date: 22 Oct 2008 - 9:00 PDT

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Argos Therapeutics today announced the publication of a paper in the October 15th issue of the Journal of Immunonology demonstrating that the Company's proprietary RNA-electroporated dendritic cells generate high-avidity cytotoxic T cells (CTL) in vitro that are able to destroy cells expressing their target antigens. This advance may potentially improve the clinical benefit of dendritic cell-based immunotherapies for the treatment of infectious disease and cancer. This approach is part of the Company's Arcelis™ technology, a proprietary platform for creating personalized immunotherapies for HIV, other infectious diseases, and cancer.

The publication describes how Argos' process of electroporating dendritic cells (DCs) with antigen-encoding RNA post-maturation, as well as co-electroporating those DCs with messenger RNA for the T cell protein CD40L (PME-CD40L process), generates CTL with the ability to rapidly proliferate, secrete pro-inflammatory mediators, and kill antigen-expressing target cells.

These DCs were shown to prime a novel subset of antigen-specific CTL that can be expanded to large numbers upon sequential DC stimulation in vitro. Argos has defined these cells as "Rapidly Expanding High Avidity" (REHA) CTL, which are characterized by the maintenance of CD28 expression required for optimal T cell activation, production of high levels of the inflammatory cytokines IFN-γ and IL-2 in response to antigen, and the demonstration of high-avidity T-cell receptors that allow efficient killing of cells bearing low levels of antigen. While the paper demonstrates that inducing REHA CTL is dependent at least in part on the production of IL-12, the neutralization of IL-12 did not affect the cytotoxic activity of REHA CTL.

"We believe that the results seen in this publication suggest that Argos' proprietary dendritic cells are uniquely capable of delivering the complex array of signals needed to generate stable and potent REHA CTL, which may confer significant immunologic benefit to dendritic cell-based immunotherapies for infectious disease and cancer," said Charles Nicolette, Ph.D., Chief Scientific Officer of Argos. "In order to be effective, these immunotherapeutics must induce robust cytotoxic T cells that can kill infected cells or tumor cells in vivo. This study shows that RHEA CTL induced by the Arcelis platform strongly favor achieving this goal."

The abstract, titled, "Priming of a novel subset of CD28+ rapidly expanding high avidity (REHA) effector memory CTL by PME-CD40L DC is IL-12 dependent," was authored by Mark A. DeBenedette, David M. Calderhead, Helen Ketteringham, Alicia H. Gamble, Joe M. Horvantinovich, Irina Y. Tcherepanova, Charles A. Nicolette and Don G. Healey.

About the Arcelis™ 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. http://www.argostherapeutics.com

Source
Jennifer Greenleaf
MacDougallvBiomedical Communications
and
Jeff Abbey
Argos Therapeutics