12) Patients who are unable to understand and sign the informed consent will be excluded 
from the study. 
13) Patients who have undergone chemotherapy will be excluded from the study 
14) No prior history of malignancy other than curatively treated non-melanoma of the 
skin or carcinoma of the cervix in-situ 
3. Justification for using subjects with compromised ability to give 
consent 
not applicable 
4. Financial considerations 
No compensation will be offered to research subjects or their families. The cost for the Clinical 
Research Center hospitalization, monitoring of patients and recording of data, and all cost for tissue 
culture and preparation of transfected cells will be borne by the study. Other costs to be charged to the 
patient's insurance would include most procedures that would be performed at this frequency in routine 
management. With the exception of the the MRI obtained on the day prior to treatment, the various 
MRI studies outlined here would be obtained during the routine followup of these patients even if they 
were they not in the study. Therefore this cost would not be considered as added expenses incurred by 
participation in the study. 
IV. Risks and benefits 
Risk/Benefit Ratio 
Benefits : The curative effects of this therapy in rats may not be transferable to the humans 
because of basic differences between rat and human glial tumors and immune systems. Alternatively, 
patients may already be so immunosuppressed by their neoplasms that they cannot mount a response 
sufficient to impact the existing tumor burden. However, this therapy might be effective despite 
theoretical obstacles. Therefore, the major potential benefit of this study to a glioma patient will be 
the development of an effective immunotherapy which will result in the regression of his or her tumor. 
This approach to active immunization could provide lasting and sustained anti-tumor effects, in 
contrast to other models of immune therapy which are time-limited and require harvesting of large 
quantities of the patient's own immune cells (41). New knowledge gained in the area of tumor 
immunology and the interaction of tumor and host will provide another potential benefit. Finally, 
studies such as this one provide psychological benefit to patients with fatal diseases by giving them a 
sense of hope and of active participation in therapy, as well as by creating an altruistic outlet. 
Risks and Precautions to minimize risks: One potential adverse effect could be the 
development of focal peri-tumoral cerebral edema. Study patients may have significant residual or 
recurrent tumor mass at the time of antisense treatment. If injection of transfected tumor cells provokes 
an immune-mediated lytic response against tumor cells, release of various mediators and associated 
tumor necrosis could provoke a temporary worsening of pre-existing tumor swelling or vasogenic cerebral 
edema. If severe, a shift in neural structures could worsen a pre-existing neurologic deficit and even 
lead to coma or death. Therefore, patients will be followed closely with serial neurologic 
examinations and MRI studies. Despite the availability of this imaging modality, it may not be 
possible to distinguish worsening due to growth of the tumor fi «.m that due to cerebral edema in response 
to changes in the tumor induced by the antisense therapy. If worsening of the neurologic status 
specifically due to increased focal cerebral edema develops, the patient will be treated with high- 
potency glucocorticoids (Decadron). If the patient is already on these agents the dose will be increased 
Recombinant DNA Research, Volume 18 
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