Local Injection Site Special attention will be given to measuring and monitoring the forearm 
site of injection for evidence of tumor growth, inflammation, or infiltration. Injection sites will be 
graded on a simple 0 to 4+ scale for evidence of inflammation or ulceration (See Attachment C). Local 
wound care will be provided if indicated. Since injected cells will have been irradiated, growth of a 
tumor mass at the injection site will be very unlikely. However, the original injection site in the 
forearm will be biopsied at four weeks and examined histologically for evidence of tumor reocurrence or 
(as expected) infiltration with immune cells. 
Neurologic Examinations. Although no direct manipulation of neural tissue is involved, 
it is possible that an immune-mediated response to the tumor could produce peri-tumoral cerebral 
edema with transient or permanent neurologic deficit. Such a reaction is likely to occur between one and 
four weeks following injection. Therefore patients will be evaluated with serial neurologic and 
physical exams. Results of these exams will be compiled and maintained in a file by the data 
coordinator for this study. Patients and their families will be advised regarding neurologic changes for 
which they should call the attending neurosurgeon. Any report of decreased neurologic function will be 
cause for immediate neurologic examination and repeat MRI scan. In addition, followup MRI scans will 
be obtained regardless of neurologic function at 8 weeks and again at 4 months visit. The examining 
physician will be looking for evidence of infection or activation of Epstein/Bar infection and will be 
especially alert to any evidence of fever or neurologic deterioration which could signify autoimmune 
demyelinating encephalitis. If the latter is suspected appropriate diagnostic and clinical managment 
steps will be offered, including rebiopsy and increased glucocorticoid therapy if necessary. 
Performance Rating s. Psychometric testing and scoring using a Kamofsky performance score 
will be performed before surgery, at the start of the trial, at four weeks, then every other month. In 
addition to the Kamofsky functional ratings (See Attachment A), patients will be evaluated in the 
Neurooncology clinic using the Levin scale (Attachment B; 49). These ratings will be applied to major 
categories such as area of tumor enhancement on MRI, mental status, motor function, seizure frequency, 
sensory abnormalities, gait, and overall clinical impression. 
Laboratory Studies: The following laboratory evaluation will be performed when a patient 
is entered into the study: CBC with differential, Epstein-Barr virus titer, HIV antibody screen, 
CD4/CD8 ratio, serum immunoglobulin levels and a routine chemistry panel including BUN, creatinine, 
and liver function studies (SMA-18). At each visit described above the following will be repeated: CBC 
with differential, C4/C8 suppressor cell ratios, routine chemistry panel. Patients will receive skin 
testing with a panel for delayed type hypersensitivity (Tb, Mumps, Candida, Trychophyton 
Diptheria Toxin, and control) before surgery and at the end of the study (six months). Chest X-Ray will 
be performed at the time of admission and at 4 months. 
NeuroRadiologic Studies Magnetic Resonance Image (MRI) scanning with and 
without Gadolinium contrast will be performed as part of routine management in these patients before 
surgery and after completion of radiation therapy (also the beginning of the clinical trial). Patients 
will be evaluated with pre- and post-procedure MRI. MRI will be repeated at 8 weeks and 4 months. 
Chest X-Ray will be performed at the time of MRI. 
Other Studies. As part of this study the patient will be asked to undergo phlebotomy of 50 
ml of whole blood at four to six weeks after surgery. Cells will be centrifuged and the buffy coat layer 
of white blood cells retrieved. Culture of glial tumor cells will be divided into two portions. One 
portion will be transfected with plasmid containing antisense to IGF-I, and stable transfectants will be 
derived by selection with the antibiotic Hygromycin®. The other portion of glial cells, derived from 
the parental culture, will serve as control. Both a culture of transfected cells as well as the non- 
transfected line will be irradiated with 5000 cGy from a cobalt source. This treatment has been shown 
to result in cells that do not divide and do not incorporate tritiated thymidine into DNA. The 
irradiated and transfected culture will be co-incubated with the buffy layer containing lymphocytes, 
helper cells and other components of the immune system that facilitate activation of T lymphocytes. If 
such coincubation results in incorporation of tritiated thymidine into DNA it would be a clear 
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Recombinant DNA Research, Volume 18 
