Non-Technical Abstract 
Protocol Title: Clinical Protocol for Modification of Tumor Suppressor 
Gene Expression and Induction of Apoptosis in Non-Small 
Cell Lung Cancer (NSCLC) with an Adenovirus Vector 
Expressing Wildtype p53 and Cisplatin 
Principal Investigator: Jack A. Roth, M.D. 
The purpose of this protocol is to study a way of stopping cancer causing 
genes from functioning in human lung cancer cells in patients. One gene that is 
commonly altered in human lung cancer is the p53 tumor suppressor gene. A 
mutation or deletion of both copies of this gene causes the cell to become 
cancerous. 
This protocol uses a gene therapy technique to replace the normal function 
of the p53 gene. The normal p53 gene will be introduced into lung cancer cells. 
This normal gene will overcome the function of the mutant gene and also replace 
the normal p53 function. 
A novel feature of this protocol is that the gene will be introduced into 
human cancer cells in the patient by an adenovirus. A special adenovirus that is 
harmless to patients and rendered incapable of dividing is used. The adenovirus is 
taken up by the cancer cell but is not integrated into the cancer cell's DNA. The 
newly inserted gene is now expressed for a short period of time. This burst of 
expression by the p53 gene renders the cancer cell incapable of growing and 
dividing and the cell initiates a program that leads to its death. A common 
chemotherapy agent (drug) called cisplatin will be given along with the adenovirus. 
The adenovirus potentiates the cancer killing ability of this drug. The normal p53 
gene is not harmful to normal cells. The adenovirus will be injected directly into 
the lung cancer. 
Patients with lung cancer who are unable to have surgery, radiation therapy, 
or chemotherapy may participate. The tumor will be tested to determine if it has 
one or the other genetic abnormality. The adenovirus capable of correcting the 
specific gene abnormality will be directly injected into the tumor. One injection will 
be of the adenovirus alone and the second injection will be of the adenovirus 
followed by intravenous administration of the cisplatin. Following this the growth 
of the tumor will be measured. The tumor will also be studied to determine if the 
tumor cells are taking up the adenovirus. 
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Recombinant DNA Research, Volume 19 
