Interleukin-10 enhances the therapeutic effectiveness of a recombinant poxvirus-based vaccine in an experimental murine tumor model.
Interleukin-10 (IL-10) has a wide range of in vivo biological activities and is a key regulatory cytokine of immune-mediated inflammation. The authors found that murine IL-10 given 12 hours after a recombinant vaccinia virus (rVV) containing the LacZ gene significantly enhanced the treatment of mice bearing 3-day-old pulmonary metastases expressing beta-galactosidase. Because IL-10 has been shown to inhibit the functions of key elements of both innate and acquired immune responses, the authors hypothesized that IL-10 might act by inhibiting clearance of the rVV, thus prolonging exposure to the experimental antigen. However, evidence that IL-10 was not acting primarily through such negative regulatory mechanisms included the following: (a) IL-10 also enhanced the therapeutic effectiveness of a recombinant fowlpox virus, which cannot replicate in mammalian cells; (b) Titers of rVV in immunized mice were lower, not higher; and (c) Although IL-10 did not alter levels of anti-vaccinia anti-bodies or natural killer cell activity, rVV-primed mice treated with IL-10 had enhanced vaccinia-specific cytotoxic T-lymphocyte activity. Thus, IL-10 enhanced the function of a recombinant poxvirus-based anti-cancer vaccine and may represent a potential adjuvant in the vaccination against human cancers using recombinant poxvirus-based vaccines.
Kaufman
H L
HL
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Rao
J B
JB
Irvine
K R
KR
Bronte
V
V
Rosenberg
S A
SA
Restifo
N P
NP
Irivine
K R
KR
D000230:Adenocarcinoma / Q000628:therapy; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000628:therapy; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000627:therapeutic use; D007700:Kinetics; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014614:Vaccines, Synthetic / Q000627:therapeutic use*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D014614:Vaccines, Synthetic; D016753:Interleukin-10; D001616:beta-Galactosidase