evaluated in 1973 by Couch et al. (1973). In those studies normal adults were immunized 
with Ad5 capsid antigens and later exposed to an inoculum of wild type Ad5 into the 
respiratory tract. Only ten of nineteen individuals who received placebo immunization 
developed symptoms and these were only mild fevers and moderate pharyngitis. No other 
effects were noted. Similar considerations are used to evaluate the potential risk to health 
care workers involved in this trial should there be a break in the containment protocol. 
Therefore, we believe the use of Ad5 as the parent vector for this protocol poses a very 
limited risk to the patient, their family, and healthcare personnel. 
The vector proposed for this trial, ADV/RSV-tk, adds only incremental changes to 
those used in previous RAC approved gene therapy protocols. It is an adenoviral vector 
similar to those being used in cystic fibrosis treatment trials (RAC 9212-034, 9212-035, 
9212-036, 9303-041, 9303-042, 9312-067). However, for example, instead of the CFTR 
gene driven by a chick B actin promoter and CMV enhancer (RAC 9212-035), AdV/RSV-tk 
contains the Herpes simplex virus thymidine kinase (HSV-tk) gene driven by the Rous 
sarcoma virus long terminal repeat (RSV-LTR). The HSV-tk gene is currently being used in 
retroviral vectors in various RAC approved protocols (RAC 9206-019, 9303-037, 9306-050, 
9309-055) for treatment of solid tumors similar to those proposed here. ADV/RSV-tk has 
been extensively analyzed for efficacy in vitro and in small animal protocols and for safety in 
primate studies (see below). Details of its construction are provided in Appendix C. 
F. Preparation of ADV/RSV-tk Adenovirus Vector 
The ADV/RSV-tk adenovirus vector will be prepared in Baylor College of Medicine's 
Gene Vector Lab using Good Laboratory Practices. (Appendix C) 
V. Potential Hazards 
A. Potential Surgical Complications 
The risks associated with the surgical portion of the procedure are similar to those 
encountered in stereotactic biopsy of tumors. The risk depends on the preoperative 
condition of the patient, size and location of the tumor, and associated diseases. The 
individual risk will be determined prior to the decision to perform the therapy and will be 
discussed with the patient prior to surgery. Specific surgical complications include: 
1 . Infection: Surgical wound infection after craniotomy occurs in less than 1% of our 
patients. Antibiotic therapy will be given as a prophylaxis prior to the surgical 
interventions and as medically indicated. 
2. lncreased ICP: Patients with brain tumors may have increased intracranial pressure 
(ICP). Patients will be treated with dose dexamethasone given in a standard 
manner for neurosurgical patients. Additional measures such as mannitol 
administration may be given. 
3. Cerebral Edema: Edema secondary to necrosis and destruction of the tumor may 
occur. The magnitude of such edema, if it occurs, is unknown. As a precaution, 
patients will be treated with steroids. 
4. Seizure: Phenytoin will be used as the primary anticonvulsant drug, unless 
contraindicated, in standard peri-operative neurosurgical doses. 
Recombinant DNA Research, Volume 20 
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