Anti-CD3/anti-CD28 monoclonal antibody-coated suture enhances the immune response of patients with head and neck squamous cell carcinoma

Objective: To test whether anti-CD3/anti-CD28 (alpha CD3/alpha CD28) monocl onal antibodies could be coated on surgical suture and used to enhance T-ce ll immune function in patients with advanced-stage head and neck squamous c ell carcinoma (HNSCC). Design: alpha CD3/alpha CD28 monoclonal antibodies at varying concentration s and ratios were coated on surgical sutures and tested on peripheral blood mononuclear cells from normal donors to identify the optimal stimulating c ondition. Immune-enhancing properties of alpha CD3/alpha CD28 monoclonal an tibody suture were tested on peripheral blood mononuclear cells and regiona l lymph node mononuclear cells isolated from patients with advanced HNSCC a nd on normal donor peripheral blood mononuclear cells. Proliferation, T-cel l phenotype, and cytokines were measured during 8-day in vitro stimulation with alpha CD3/alpha CD28 suture and compared with alpha CD3/alpha CD28-coa ted tissue culture plastic, a previously recognized carrier. Results: Optimal stimulation was observed with mono-filament nylon incubate d with alpha CD3/alpha CD28, 2 mu g/mL, at a 1:1 ratio for 18 hours at 37 d egrees C. Strong proliferation of peripheral blood mononuclear cells and ly mph node mononuclear cells in patients with HNSCC was induced by alpha CD3/ alpha CD28 suture. There was no difference in maximal proliferation between alpha CD3/alpha CD28 plastic and suture. On day 6 after alpha CD3/alpha CD 28 suture stimulation, T-cell subpopulations expressing CD3, CD4, CD8, CD28 , and CD45RO were enhanced. Suture stimulation significantly enhanced inter leukin 2 secretion when compared with plastic stimulation (P = .01). Both a lpha CD3/alpha CD28 suture and plastic stimulated interferon gamma secretio n. Conclusions: To our knowledge, this study is the first to report the modifi cation of surgical suture to create an immunomodulant. alpha CD3/alpha CD28 -coated suture expanded T cells from patients with HNSCC and induced a T(H) 1 immune response, which may be a useful therapeutic tool in the treatment of HNSCC and other diseases.