A final potential risk is the failure of the transfected cells to elicit any response at all, due to 
inadequate doses of transfected cells or local host factors. The site of subcutaneous injection in each case 
will be the forearm, because this site has previously been shown to result in more effective antibody 
formation with traditional immunization for pneumococcal and hepatitis vaccine. 
Human applications of gene therapy for cancer are very few at present. This project may offer 
some theoretical advantages when compared to human trials of gene therapy already ongoing. First, 
the transfected tumor cells will be injected into a subcutaneous site which can be readily observed, and 
even totally resected if necessary. Second, we are using human, not animal cells, at a site distant from 
the brain. Repeat surgery or stereotactic placement of the transformed cells will not be required. 
Thirdly, the effector limb of this therapy is the tumor patient's own immune system. No exogenous 
medications such as IL-2 or gangciclovir will be required to produce the desired therapeutic effect in the 
transfected cells. Therefore the drug toxicity associated with such agents is eliminated. 
Monitoring of Toxicitv/Reporting of Adverse Reactions/Stop Criteria: 
Potential complications and toxicities and approaches to their control were described in the previous 
section. Any significant deterioration in mental status or neurological function, or evidence for altered 
immunity and/or infection that is not readily attributable to the underlying disease process will be 
cause to interrupt the study for all subsequent patients. Examples of such changes would include: 
1. Infection at the site of injection 
2. growth of tumor at the site of injection 
3. deterioration in neurologic function not attributed to normal progression of tumor growth or to 
other metabolic or systemic derangements 
4. an immune reaction not attributable to drugs or medications 
5. sudden unexplained death 
The adverse reactions would be reported promptly to the Investigational Drug Branch (IDB), phone 
(301) 496-7957. ADR reports will be made even if there is only a suspicion of an adverse effect. Life- 
threatening reactions and/or deaths while on treatment will be reported to the NCI by phone within 24 
hours. A written report will follow within 10 working days. Written reports will be sent to 
Investigational Drug Branch Cancer Therapy Evaluation Program P.O. Box 30012 Bethesda, MD 20824. 
The course of the study would remain interrupted until a review of the circumstances involved has been 
made by the primary investigators and the Gene Therapy Subcommittee of the Ireland Cancer Center at 
Case-Western Reserve University, and until appropriate solutions to the problem have been 
determined. 
V. Justification of Study 
The success in treatment of glioma has not increased significantly over the past several 
decades. The only success achieved is a modest increase in longevity and this is dependent upon radical 
excision of early and anatomically accessible lesions. The overall survival remains dismal and the 
disease is almost uniformly fatal. These statistics warrant an aggressive search for new therapies. The 
data presented here in studies using an anti-sense IGF-I strategy in treatment of rat glioblastoma 
represent a unique approach to the induction of the immune system. The results merit a trial of the same 
strategy in human subjects. 
Recombinant DNA Research, Volume 18 
[143] 
