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Terry Y. Shibuya, MD; Wei-Zen Wei, PhD; Michelle Zormeier, MD; John Ensley, MD; Wael Sakr, MD; Robert H. Mathog, MD; Robert J. Meleca, MD; George Yoo, MD; Carl H. June, MD; Bruce Levine, PhD; Lawrence G. Lum, MD

Arch Otolaryngol Head Neck Surg. 1999;125:1229-1234.

Objective  To test whether anti-CD3/anti-CD28 (CD3/CD28) monoclonal antibodies could be coated on surgical suture and used to enhance T-cell immune function in patients with advanced-stage head and neck squamous cell carcinoma (HNSCC).

Design  CD3/CD28 monoclonal antibodies at varying concentrations and ratios were coated on surgical sutures and tested on peripheral blood mononuclear cells from normal donors to identify the optimal stimulating condition. Immune-enhancing properties of CD3/CD28 monoclonal antibody suture were tested on peripheral blood mononuclear cells and regional lymph node mononuclear cells isolated from patients with advanced HNSCC and on normal donor peripheral blood mononuclear cells. Proliferation, T-cell phenotype, and cytokines were measured during 8-day in vitro stimulation with CD3/CD28 suture and compared with CD3/CD28-coated tissue culture plastic, a previously recognized carrier.

Results  Optimal stimulation was observed with monofilament nylon incubated with CD3/CD28, 2 µg/mL, at a 1:1 ratio for 18 hours at 37°C. Strong proliferation of peripheral blood mononuclear cells and lymph node mononuclear cells in patients with HNSCC was induced by CD3/CD28 suture. There was no difference in maximal proliferation between CD3/CD28 plastic and suture. On day 6 after CD3/CD28 suture stimulation, T-cell subpopulations expressing CD3, CD4, CD8, CD28, and CD45RO were enhanced. Suture stimulation significantly enhanced interleukin 2 secretion when compared with plastic stimulation (P=.01). Both CD3/CD28 suture and plastic stimulated interferon secretion.

Conclusions  To our knowledge, this study is the first to report the modification of surgical suture to create an immunomodulant. CD3/CD28-coated suture expanded T cells from patients with HNSCC and induced a T_H1 immune response, which may be a useful therapeutic tool in the treatment of HNSCC and other diseases.

From the Departments of Otolaryngology–Head and Neck Surgery (Drs Shibuya, Zormeier, Mathog, Meleca, and Yoo), Immunology/Microbiology (Dr Wei), Medicine (Dr Ensley), and Pathology (Dr Sakr), Wayne State University School of Medicine, and the Karmanos Cancer Institute (Drs Wei, Ensley, and Sakr), Detroit, Mich; the Naval Medical Research Institute, Bethesda, Md (Drs June and Levine); and the Immunotherapy Research and Treatment Institute, St Luke's Medical Center, Milwaukee, Wis (Dr Lum).

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