Recombinant DMA Advisory Committee- 9/12-13/94 
Dr. Albelda said that GCV is a better substrate for the HSV-TK enzyme than ACV. 
Since this study is of a new therapy, he did not want to introduce another parameter to 
change the generally accepted use of GCV. He agreed it is worthwhile to explore other 
drugs if the strategy is proven to be useful for the treatment of cancer. 
Dr. Albelda agreed to revise the Informed Consent document to delete the exclusion 
criteria regarding prior gene therapy and other items suggested by the RAC. 
Dr. Albelda will revise the management schedule for GCV toxicity. He made a comment 
about the vector-induced inflammation. Inflammation in a closed space of the brain is 
undesirable; however, it is acceptable and is actually intended as a form of 
immunotherapy for pleural cancer. Perhaps inducing inflammation may induce a more 
therapeutic response in tumors. It should not cause any problem for the pleural space. 
Nevertheless, signs of inflammatory response is one of the major endpoints of the human 
studies with the adenovirus vectors. Pleural tissues obtained by biopsy following vector 
administration will be examined by immunohistochemistry for signs of inflammation. The 
presence and expression of the transgene will be studied. An important aspect about the 
protocol is that a surgeon can easily access the pleural space to obtain biopsy samples for 
detailed studies to learn more about the scientific problems of host-vector interactions in 
the adenovirus vector system. 
Dr. Wilson said that the compiled DNA sequences can account for all the components of 
DNA fragments, and they are in the process of completing actual sequencing of the entire 
vector DNA. 
Dr. Treat accepted the GCV dose modifications as suggested by Dr. Straus. Addressing 
the question of prior therapies, Dr. Treat said that the major reason to exclude 
radiotherapy patients is the formation of adhesion or sclerosis of pleural cavity that can 
result from previous treatments. This mechanical problem will prevent successful 
placement of a chest tube. As to the chemotherapy patients, they may have worse 
performance status and overall condition. Gene therapy exclusion will be deleted. 
Regarding the concern of at least 9 chest X-ray examinations for each patients, Dr. Lavi, a 
co-investigator, commented that the total exposure of 10 chest X-rays would only be one 
10th of the radiation exposure allowed by the FDA rule. He considered it is a safe level 
of radiation. 
Dr. Albelda said that patients enrolled in this study will not be precluded from any other 
future treatments including surgical procedures, chemotherapy or radiotherapy. He said 
he would agree to expand the statement in the Informed Consent document that the long- 
term effects of gene therapy are unknown. Mr. Capron said that the Informed Consent 
document would be preferable if the whole consent form were written with the 
investigators in the first person (I or we) and the subject as the second person (you) 
because of the complicated nature of the information. Dr. Albelda agreed to these 
suggestions. 
[82] 
Recombinant DNA Research, Volume 20 
