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Bioactive Suture

A Novel Immunotherapy for Head and Neck Cancer

Departments of ¹ Otolaryngology/Head & Neck Surgery and ² Urology, University of California Irvine College of Medicine, Orange, California; ³ Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, California; ⁴ Boston University School of Medicine, Boston, Massachusetts; ⁵ Epidemiology Division, Department of Medicine, University of California Irvine, Irvine, California; and ⁶ Department of Otolaryngology, Wayne State University School of Medicine, Detroit, Michigan

Purpose: We have proposed to characterize the mechanism through which bioactive surgical sutures generate a T_H1 immune response and to define the immune-stimulating half-life of the sutures.

Experimental Design: Bioactive sutures of interferon (IFN), interleukin 2 (IL-2), anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFN sutures were used to stimulate lymphocytes from normal donors and from head and neck cancer patients in vitro over a 24-day period. Cell supernatants were analyzed by ELISA, and T cells were phenotyped to characterize the immune response generated. Intracellular cytokine staining was performed to measure the expansion of flu-specific T cells. Electromobility shift assay and supershift assay were used to measure the intranuclear DNA binding activity of nuclear factor B and its p65 subunit in T cells activated by sutures in the presence and absence of a proteasome inhibitor, MG-132.

Results: Anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFN generated a prolonged T_H1 immune response for 18 days in vitro. Anti-CD3/CD28 expanded flu-specific T cells. Activated T cells demonstrated enhanced CD40 ligand (CD40L) expression within 72 hours of stimulation, which stimulated other cells to secrete IL-12. Stimulated T cells demonstrated increased intranuclear expression of nuclear factor-B, which was blocked by MG-132, and also reduced CD40L and IL-12 expression.

Conclusions: This is the first report to demonstrate that bioactive surgical sutures can generate a prolonged T_H1 immune response and expand flu-specific T cells. Bioactive sutures, which are primarily a T-cell stimulant, also stimulated other cells to secrete IL-12 and prolonged the immune response. Sutures may provide a novel in situ stimulating strategy for enhancing the immune system of cancer patients.