—In Vitro Results Published in Journal of Immunotherapy Demonstrate That Potency of Mature CD40L RNA Electroporated DCs Correlates with IL-12 Secretion by Tracking Multifunctional CD8(+)/CD28(+) Cytotoxic T-cell Responses—
Durham, NC– January 31, 2011 – Argos Therapeutics announced today that interleukin (IL)-12 secretion can predict the potency of the company’s Arcelis™ 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-γ and tumor necrosis factor-α 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-γ and tumor necrosis factor-α. 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.