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

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.

• Authors: James E Egan, Karen J Quadrini, Frances Santiago-Schwarz, John W Hadden, Harvey J Brandwein, Kathy L Signorelli
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) Vol. 30 Issue 6 Pg. 624-33 (Sep 2007) ISSN: 1524-9557 [Print] United States
• PMID: 17667526 (Publication Type: Journal Article)

Chemical References

• Antigens, CD
• CCR7 protein, human
• Cytokines
• IRX 2
• Receptors, CCR7
• Receptors, Chemokine
• Interleukin-12

Topics

• Antigens, CD (metabolism)
• Cell Differentiation
• Cell Shape (drug effects)
• Cytokines (immunology, pharmacology)
• Dendritic Cells (cytology, drug effects, immunology, metabolism)
• Endocytosis (drug effects)
• Humans
• Interleukin-12 (immunology, metabolism)
• Lymphocyte Activation
• Lymphocyte Culture Test, Mixed
• Monocytes (cytology, drug effects, immunology)
• Receptors, CCR7
• Receptors, Chemokine (metabolism)
• T-Lymphocytes (immunology)