title: Anti-CD3/anti-CD28 monoclonal antibody-coated suture enhances the immune response of patients with head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  To test whether anti-CD3/anti-CD28 (alphaCD3/alphaCD28) 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).
  
  
  METHODS
  AlphaCD3/alphaCD28 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 alphaCD3/alphaCD28 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 alphaCD3/alphaCD28 suture and compared with alphaCD3/alphaCD28-coated tissue culture plastic, a previously recognized carrier.
  
  
  RESULTS
  Optimal stimulation was observed with monofilament nylon incubated with alphaCD3/alphaCD28, 2 microg/mL, at a 1:1 ratio for 18 hours at 37 degrees C. Strong proliferation of peripheral blood mononuclear cells and lymph node mononuclear cells in patients with HNSCC was induced by alphaCD3/alphaCD28 suture. There was no difference in maximal proliferation between alphaCD3/alphaCD28 plastic and suture. On day 6 after alphaCD3/alphaCD28 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 alphaCD3/alphaCD28 suture and plastic stimulated interferon gamma secretion.
  
  
  CONCLUSIONS
  To our knowledge, this study is the first to report the modification of surgical suture to create an immunomodulant. AlphaCD3/alphaCD28-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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Wayne State University School of Medicine, Detroit, Mich 48201, USA. ShibuyaT@Karmanos.org
authors.forename: T Y
authors.initials: TY
authors.lastname: Shibuya
authors.forename: W Z
authors.initials: WZ
authors.lastname: Wei
authors.forename: M
authors.initials: M
authors.lastname: Zormeier
authors.forename: J
authors.initials: J
authors.lastname: Ensley
authors.forename: W
authors.initials: W
authors.lastname: Sakr
authors.forename: R H
authors.initials: RH
authors.lastname: Mathog
authors.forename: R J
authors.initials: RJ
authors.lastname: Meleca
authors.forename: G
authors.initials: G
authors.lastname: Yoo
authors.forename: C H
authors.initials: CH
authors.lastname: June
authors.forename: B
authors.initials: B
authors.lastname: Levine
authors.forename: L G
authors.initials: LG
authors.lastname: Lum
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D016207:Cytokines / Q000276:immunology; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008875:Middle Aged; D009367:Neoplasm Staging; D009757:Nylons; D010641:Phenotype; D010969:Plastics; D013537:Sutures; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D020099:Coated Materials, Biocompatible; D016207:Cytokines; D007376:Interleukin-2; D009757:Nylons; D010969:Plastics; D007371:Interferon-gamma