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IL-12 Treatment of Endogenously Arising Murine Brain Edward J. Roy,2

Summary: IL-12 Treatment of Endogenously Arising Murine Brain
Edward J. Roy,2
* Ute Gawlick,* Brent A. Orr,* Laurie A. Rund,
Andrew G. Webb,
David M. Kranz
A number of recent studies have indicated that T cells can be stimulated to attack transplanted brain tumors in rodent models.
As IL-12 has been shown to activate cytotoxic T cell responses, we tested the idea that it might stimulate a T cell response against
endogenous brain tumors that arise in SV40 large T Ag transgenic mice (SV11). SV11 mice develop tumors of the choroid plexus,
a specialization of the ependymal lining of the brain ventricles. They are a particularly relevant model of human disease, because
they are immunocompetent but immunologically tolerant of the tumors. SV11 mice were treated with recombinant murine IL-12
for 10 days. Tumors grew more slowly than in control treated mice, and in some cases were reduced in size, as assessed by magnetic
resonance imaging before and after treatment. At the end of treatment, tumors, but not brain parenchyma, exhibited extensive
infiltration of activated CD8 and CD4 T cells. Tumors also showed a reduction in vascular density. Mice treated with IL-12
lived significantly longer than control mice. Tumors that progressed were nearly devoid of T cells, indicating that the T cell
response was not sustained. In addition, some mice that had a substantial tumor burden at the beginning of treatment displayed
evidence of immunosuppression, which might be related to TGF- 2 detected in tumors. We conclude that IL-12 treatment can
initiate an anti-tumor response even against endogenously arising brain tumors, but factors that will allow a sustained and more
effective anti-tumor response need to be determined. The Journal of Immunology, 2000, 165: 72937299.


Source: Andrews, Anne M. - Huck Institutes of the Life Sciences, Pennsylvania State University


Collections: Biology and Medicine