IL-2 doses >100 units/24 hrs. Therapy with tamoxifen (80 mg BID) was initiated approximately 3 months 
after the first immunization. This agent has inhibited tumor growth in some GBM patients. MRI scans 
performed at approximately 4 week intervals during the first five months of treatment revealed modest 
changes in overall tumor size with waxing and waning of peritumoral edema associated with alterations in 
decadron doses. The MRI scan performed six months after the initiation of treatment (4 weeks after the 
highest dose IL-2 immunization) revealed marked tumor necrosis with significant peritumoral edema 
(Figure 4). Clinically, these MRJ findings were associated with an exacerbation of the patient's baseline 
left sided weakness. This gradually resolved following the administration of increased decadron doses 
which have been gradually tapered. Stereotactic intraventriculostomy was performed to relieve increased 
pressure in the left third ventricle. Cytological evaluation of cerebrospinal fluid revealed the presence of 
inflammatory cells without detectable tumor cells. The patient received no further treatment until 2 
months later when the MRJ scan revealed renewed tumor growth (8 months after the initiation of 
treatment). At this time, the patient was injected with a combination of transduced tumor cells and 
fibroblasts and non-transduced tumor cells to yield an IL-2 dose of 1 10 units/24 hrs. The clinical course 
of the patient is described in detail in Appendix 12.8. 
In summary, IL-2 gene therapy resulted in no significant toxicity at the sites of immunization and was 
associated with the generation of a cellular anti-tumor immune response. Marked tumor necrosis was 
observed following the highest IL-2 immunization dose. It is not possible to draw meaningful 
conclusions regarding safety, efficacy or immune response induction from the results of a single patient. 
However, we are encouraged by these preliminary findings and believe that they warrant evaluation of EL- 
2 gene therapy in additional GBM patients as outlined in this protocol. 
Recombinant DNA Research, Volume 19 
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