Interleukin (IL)-12 Secretion Can Predict Potency of Argos Therapeutics’ Arcelis(TM) Dendritic Cell (DC) Immunotherapy and Can Be Used as Potency Marker in Phase 3 Clinical Trial
DURHAM, N.C., Jan. 31, 2011 /PRNewswire/ — Argos Therapeutics announced today that interleukin (IL)-12 secretion can predict the potency of the company’s Arcelis(TM) dendritic cell (DC) immunotherapy and can be used as a potency marker in a Phase 3 clinical trial testing the company’s lead product, AGS-003, in metastatic renal cell carcinoma (mRCC). In vitro results published in the Journal of Immunotherapy demonstrate that the potency of mature CD40L RNA electroporated DCs correlates with IL-12 secretion by tracking the multifunctional CD8(+)/CD28(+) memory T-cell responses.
“The dependence of AGS-003-induced memory cytotoxic T lymphocytes on IL-12 secretion from DCs makes it an attractive marker for DC potency,” said Charles Nicolette, Ph.D., chief scientific officer and vice president of research and development of Argos. “Using IL-12 secretion as a potency marker is highly relevant to AGS-003 since it is directly linked to the mechanism of action and it is equally relevant to other Arcelis products such as AGS-004 for HIV.”
Jeff Abbey, president and chief executive officer of Argos, added, “Identifying an effective potency marker for our upcoming Phase 3 clinical trial in mRCC is a significant step in the advancement of our pipeline. We are in the process of securing funding to begin the trial by mid-2011. Our Arcelis HIV program is currently being tested in a Phase 2b study co-funded by the NIH.”
Electroporation of mature DCs with RNA-encoding CD40L greatly enhances the production of IL-12, a proinflammatory cytokine necessary for the induction of T-cell immunity. In vitro results presented in the Journal of Immunotherapy reveal a correlation between the priming of CD28(+) antigen-reactive effector memory CTL displaying three or four simultaneous effector functions and the quantity of IL-12 produced by post-maturation RNA electroporated DC. By using multiparameter flow cytometry, the quantities of IL-12 needed to prime naive antigen-reactive T cells to simultaneously produce interferon-gamma and tumor necrosis factor-alpha in the presence or absence of IL-2 secretion in conjunction with lytic activity defined by CD107a expression can be used to determine the overall potency of a DC product. In the presence of IL-12, CTL differentiation toward lytic function is not accompanied by a reduction in the secretion of interferon-gamma and tumor necrosis factor-alpha. Therefore, by measuring the availability of IL-12 one can predict the potency of a DC immunotherapeutic in relation to its ability to drive distinct effector memory CTL subsets with multifunctional activities.
Arcelis is Argos’ proprietary technology for personalizing RNA-loaded dendritic cell immunotherapies for cancer, HIV and other infectious diseases. This platform is based on optimizing a patient’s own (autologous) dendritic cells to trigger a tumor- or pathogen-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 the patient’s 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.
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
Contacts: --------- David Schull or Andreas Marathovouniotis Russo Partners LLC (212) 845-4271 or (212) 845-4235 firstname.lastname@example.org or email@example.com Jeff Abbey Argos Therapeutics (919) 287-6308 firstname.lastname@example.org
SOURCE Argos Therapeutics, Inc.