Bioactive suture: a novel immunotherapy for head and neck cancer.
OBJECTIVE
We have proposed to characterize the mechanism through which bioactive surgical sutures generate a T(H)1 immune response and to define the immune-stimulating half-life of the sutures.


METHODS
Bioactive sutures of interferon gamma (IFNgamma), interleukin 2 (IL-2), anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma 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 kappaB 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 + IFNgamma generated a prolonged T(H)1 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-kappaB, 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(H)1 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.
Shibuya
Terry Y
TY
Department of Otolaryngology/Head & Neck Surgery, University of California Irvine College of Medicine, Orange, California 92868, USA. tshibuya@uci.edu
Kim
Sanghun
S
Nguyen
Kevin
K
Do
Johnny
J
McLaren
Christine E
CE
Li
Kuo-Tung
KT
Chen
Wen-Pin
WP
Parikh
Parag
P
Wadhwa
Ashish
A
Zi
Xiaolin
X
Chen
Vincent Y
VY
Wong
Hau-Sin
HS
Armstrong
William B
WB
Yoo
George H
GH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001672:Biocompatible Materials; D016207:Cytokines / Q000008:administration & dosage* / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013536:Suture Techniques; D013601:T-Lymphocytes / Q000276:immunology*
D001672:Biocompatible Materials; D016207:Cytokines