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Cytokine
Immuno-Gene Therapy for Treatment of Brain Tumors
Terry
Lichtor, Roberta P. Glick
Department
of Neurological Surgery, Rush Medical College, Cook County Hospital and Hektoen
Institute for Medical Research, Chicago, IL, USA
The
prognosis for patients with an intracerebral (i.c.) neoplasm is poor.
Conventional treatments such as surgery, radiation therapy and chemotherapy have
done little to affect long-term survival, and new methods of treatment are
urgently needed.
In this report approaches involving cytokine gene therapy in treatment of
malignant brain tumors are reviewed and contrasted to a strategy developed in
this laboratory involving the use of allogeneic cells genetically modified to
secrete cytokines.
In our studies, mice with an i.c. glioma, melanoma or breast carcinoma treated
solely by intratumoral injections with allogeneic cells genetically modified to
secrete interleukin-2 (IL-2) were found to survive significantly longer than
mice in various control groups.
The anti-tumor response was mediated predominantly by T-cell subsets (CD8+
and NK/LAK cells).
The injections resulted in the killing of only the neoplastic cells;
non-neoplastic cells were unaffected.
Experiments involving treatment of animals with i.c. tumor using subcutaneous
injections of cytokine-secreting allogeneic cells in the presence of tumor
antigens demonstrated no effect in prolonging survival in spite of the
development of a vigorous systemic anti-tumor immune response.
Of special interest, mice injected intracerebrally with the cytokine-secreting
allogeneic cells alone exhibited no neurologic defect and there were no adverse
effects on survival.
The injection of cytokine-secreting allogeneic cells into the microenvironment
of an i.c. tumor is hypothesized to induce an anti-tumor immune response capable
of prolonging survival.
This pre-clinical animal data directly translates into clinical treatments for
patients with a malignant i.c. tumor.
Keywords:
breast cancer, gene therapy, glioma, IL-2, tumor vaccine
Copyright
© 2003 Kluwer
Academic Publishers. All
rights reserved
Source: http://ipsapp009.kluweronline.com/content/getfile/5042/105/8/abstract.htm
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