Recombinant DNA Advisory Committee- 9/12-13/94 
sequences in gonadal tissues in the mouse experiments. The investigators have revised the 
inclusion/exclusion criteria. The exclusion criteria include patients who have had previous 
gene therapy, chemotherapy, or radiotherapy. Dr. Zallen said that there is no other gene 
therapy approved for mesothelioma. If the protocol excludes all other treated patients, 
there will be few eligible candidates left. The investigators have amended the Informed 
Consent document. The statement about research costs is now satisfactory. The usage of 
"I" and "you" is not consistent in the Informed Consent document. Dr. Joseph Treat is 
given as the investigator in the Informed Consent and yet Dr. Albelda is listed as the PI. 
It is not clear to the patients who is the physician in charge. Contraception is mentioned 
but the duration for its practice is not indicated. Dr. Zallen was concerned about the 
excessive chest X-ray to be given to the patients. 
Review-Dr. H. Ginsberg 
Dr. H. Ginsberg said that this protocol is very thoughtfully written for the treatment of 
mesothelioma. Most of his concerns have been raised in the review of the last protocol. 
He questioned if the vector produced any inflammatory response in Fisher rat 
experiments. Some of the bowel obstruction and fibrosis could have resulted from 
inflammation. Dr. H. Ginsberg suggested when tissues are obtained after vector 
administration to the patients, they should be carefully examined for signs of 
inflammation, and what multiplicity of infection of vectors will cause it. 
Other Comments 
Dr. Erickson said the present treatment is intended as the first treatment for 
mesothelioma patients and will exclude patients who have had prior treatments. He was 
concerned that the present treatment would preclude the patients from receiving other 
forms of treatment since the mesothelioma patients can have a long survival rate. Dr. 
Parkman asked the investigators to elaborate on the question if there is any pleuritis or 
pneumonitis following vector administration. Ms. Meyers said that the possible long-term 
effects and unknown side effects of gene therapy are not clearly disclosed to the patients 
in the Informed Consent document. 
Investigator Response-Drs. Albelda and Treat 
Dr. Albelda clarified that he is a pulmonary physician and is the PI of the project; and Dr. 
Treat, a medical oncologist, will supervise the clinical trial. 
Dr. Albelda presented data with a slide from a rat experiment demonstrating the absence 
of vector sequences in organs two days following vector administration to the pleural 
cavity. Vector sequences were detected by a reverse transcriptase polymerase chain 
reaction (RT-PCR) assay. No vector sequence was present in testes or ovaries. In other 
experiments, there was some uptake in tumors; and in the peritoneal model, some in liver 
and kidney probably due to mesothelial tissue that coats these organs. It should not be a 
problem for the lung. There was no toxicity found in extensive rat studies, and no vector 
sequences in gonads and all other tissues. 
Recombinant DNA Research, Volume 20 
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