Induction of Antitumor Immunity with Combination of HER2/neu DNA Vaccine and Interleukin 2 Gene-modified Tumor Vaccine
The therapeutic effects of both cytokine-secreting tumor vaccine and DNA vaccine were studied using mouse MBT-2 bladder cancer cells as a model. Cytokine-secreting MBT-2 cells were obtained by infecting cells with retroviral particles containing interleukin (IL) 2-, IL-4-, or granulocyte-macrophage...
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Published in | Clinical cancer research Vol. 6; no. 11; pp. 4381 - 4388 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Philadelphia, PA
American Association for Cancer Research
01.11.2000
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Subjects | |
Online Access | Get full text |
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Summary: | The
therapeutic effects of both cytokine-secreting tumor vaccine and DNA
vaccine were studied using mouse MBT-2 bladder cancer cells as a model.
Cytokine-secreting MBT-2 cells were obtained by infecting cells with
retroviral particles containing interleukin (IL) 2-, IL-4-, or
granulocyte-macrophage colony-stimulating factor (GM-CSF)-expression
vector. The MBT-2-IL-2 cells were not tumorigenic in syngenic C3H mice
at all. Tumor formation decreased significantly for the
MBT-2-GM-CSF cells. MBT-2-IL-2, -IL-4, and -GM-CSF cells were killed by
irradiation and tested as tumor vaccines. The irradiated MBT2-IL-2
cells could complete protect mice from the growth of the preexisting
tumor cells, and the immune memory lasted for 8 months. On the other
hand, irradiated MBT-2-IL-4 and MBT-2-GM-CSF cells were less effective.
When the loading tumor mass increased, all tumor vaccines lost
protective effects. DNA vaccine encoding the tumor antigen neu was
additionally tested to improve the therapeutic efficacy. Coinjection of
60 μg pSV-neu DNA was effective in enhancing the antitumor effects of
MBT2-IL-2; however, DNA vaccine alone cannot prevent the progression of
the preexisting tumor. Immunohistochemical analysis of tumor infiltrate
revealed massive increase of CD4 + lymphoid cells in the
group of mice treated with both DNA vaccine and IL-2-secreted tumor
vaccine. Western blotting demonstrated the presence of anti-neu
antibody in the serum from immunized mice. In contrast, combination of
DNA vaccine and MBT-2-GM-CSF has no additive effect. The results
indicate the combination of DNA vaccine and IL-2-secreting tumor
vaccine can additionally improve therapeutic efficacy, and the efficacy
is correlated with the increase of CD4 + T lymphocytes and
anti-neu antibody. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1078-0432 1557-3265 |