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J Immunother. 2007 Sep;30(6):624-33.

IRX-2, a novel in vivo immunotherapeutic, induces maturation and activation of human dendritic cells in vitro.

Author information

1
IRX Therapeutics, Inc., Farmingdale, NY 11735, USA.

Abstract

IRX-2 is a uniform, well-defined set of natural cytokines currently in Phase II clinical trials for squamous cell carcinoma of the head and neck (HNSCC). In preliminary clinical studies of HNSCC patients, IRX-2 therapy has shown promising results, increasing overall survival of patients from 32% to 61% at 48 months. Although it is known that specific cytokines in IRX-2 enhance T cell activity [e.g., interleukin-2 (IL-2), interferon-gamma, IL-1beta], we chose to investigate the influence of IRX-2 on monocyte-derived dendritic cells (Mo-DCs) isolated from human peripheral blood in an effort to further understand the clinical findings. We show here that IRX-2 treatment of human monocyte-derived DC resulted in morphologic, phenotypic, and functional changes consistent with the development of mature activated DC. Specifically, IRX-2-treated DC increased expression of CD83 and CCR7, markers for DC maturation and migration, respectively, and increased the expression of HLA-DR, CD54, and the costimulatory molecules CD86 and CD40, which are critical mediators of T cell activation. Functional changes in DC induced by IRX-2 included a reduced endocytic capacity, increased ability to stimulate T cells and increased IL-12 cytokine production. These results provide a plausible mechanistic explanation for the in vivo clinical activity of IRX-2 and an additional rationale for the use of IRX-2-based immunotherapy in patients.

PMID:
17667526
DOI:
10.1097/CJI.0b013e3180691593
[Indexed for MEDLINE]

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