EVALUATION OF CYTOKINE TOXICITY INDUCED BY VACCINIA VIRUS-MEDIATED IL-2 AND IL-12 ANTITUMOUR IMMUNOTHERAPY

Single intratumoural treatment of nude mice with a vaccinia virus (VV)-expressing interleukin-1 (IL-2) or IL-12 induced significant tumour growth inhibition associated with clear signs of toxicity. At a low virus dose, only some treated animals showed signs of toxicity. We characterized and compared...

Full description

Saved in:
Bibliographic Details
Published in:Cytokine (Philadelphia, Pa.) Pa.), 2001-09, Vol.15 (6), p.305-314
Main Authors: Chen, Bing, Timiryasova, Tatyana M., Gridley, Daila S., Andres, Melba L., Dutta-Roy, Radha, Fodor, Istvan
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - biosynthesis
Antigens, Differentiation, B-Lymphocyte - biosynthesis
B-Lymphocytes - metabolism
Cell Line
Cells, Cultured
Cytokines - genetics
Cytokines - toxicity
Fibroblasts - metabolism
Flow Cytometry
Genetic Therapy - methods
Glioma - therapy
glioma/IL-2/IL-12/toxicity/vaccinia virus
Interferon-gamma - metabolism
Interleukin-12 - genetics
Interleukin-2 - genetics
Killer Cells, Natural - metabolism
Leukocytes - metabolism
Lymphocytes - metabolism
Mice
Mice, Nude
Neoplasm Transplantation
Neoplasms - therapy
Organ Size
Rats
Receptors, Interleukin-2 - biosynthesis
Receptors, Transferrin
Spleen - metabolism
Time Factors
Transgenes
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha - metabolism
Vaccinia virus - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Single intratumoural treatment of nude mice with a vaccinia virus (VV)-expressing interleukin-1 (IL-2) or IL-12 induced significant tumour growth inhibition associated with clear signs of toxicity. At a low virus dose, only some treated animals showed signs of toxicity. We characterized and compared the activity of NK and B cells and major pro-inflammatory factors (IFN-γ, TNF-α) in treated animals with and without toxicity. One week after treatment animals exhibiting signs of cytokine-related toxicity showed dramatic increases in several measured parameters. High leukocyte and lymphocyte counts in blood and marked increases in NK and CD25+cells in both blood and spleen were associated with IL-2-induced toxicity, while IL-12-induced toxicity was related to a great elevation of CD25+cells in blood and CD71+cells in the spleen. In contrast, immune activation in animals free of toxicity was observed on day 2 after the treatment, which drastically declined by day 7. Thus, immune responses induced by IL-2 and IL-12 therapy appear to play important roles in both tumour inhibition and the accompanying toxicity. Short-term effects induced by IL-2 and IL-12 could be critical for antitumour therapy that prolongs survival and protects from adverse side effects.
ISSN:1043-4666
1096-0023
DOI:10.1006/cyto.2001.0906