Argos' AGS-004 shows feasibility in in vitro models to generate DC from viremic patients

 Argos Therapeutics announced today that its Arcelis HIV immunotherapy, AGS-004, showed feasibility in in vitro models to generate fully functional dendritic cells (DC) from viremic patients. Argos plans to start a Phase 1 trial of AGS-004 to test the prevention or delay in the initiation of antiretroviral therapy (ART) in ART-naive patients. Data were presented orally and in a poster at the HIV DART™ 2010 Conference in Los Cabos, Mexico.

"Clinical development of AGS-004 in ART-naive patients may demonstrate efficacy in delaying ART therapy," said Charles Nicolette, Ph.D., chief scientific officer and vice president of research and development of Argos. "The Phase 1 study will also evaluate whether the immunotherapy will restore the central and effector memory CD8+ T cell phenotype as demonstrated in earlier studies using product generated from leukapharesis of ART-suppressed individuals."

In a Phase 2 study, AGS-004 in combination with analytical treatment interruption was shown to delay viral rebound kinetics and significantly lower mean viral loads. These effects occurred in the absence of activation of CD4+ T cells. Immunologic activity was assessed by changes in proliferative capacity of HIV-specific CD8+ T cells and confirmed that AGS-004 was immunogenic in the majority of subjects. The predominant CD8+ central and effector memory T-cell responses induced by AGS-004 were shown to be IL-12 dependent and were comparable with profiles displayed by HIV-infected individuals defined as long-term non-progressors (CD8+, CD28+ and CD45RA-). In the study, the DCs were manufactured from monocytes collected by leukapharesis obtained from ART-suppressed individuals, and RNA was derived from their pre-ART plasma samples. This procedure was necessary because DCs generated from viremic leukaphereses were defective in IL-12 production that was shown to be caused by the viral protein R protein.

The new DC differentiation protocol usesIFNgamma, TNFalpha, and PGE(2) followed by electroporation with four RNA-encoded antigens together with RNA encoding CD40L. After further incubation for four hours, the cells wtere cryopreserved in single-dose aliquots. Products were analyzed for yield, viability, immunophenotype and cytokine production. The DC differentiation and maturation protocol for AGS-004 manufactured from treatment naive viremic patients resulted in matured DCs secreting IL-12 and was indistinguishable from products generated from ART-suppressed or healthy subjects.

Source:

Argos Therapeutics, Inc.

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