Non -Technical Abstract 
NON-TECHNICAL ABSTRACT 
Neuroblastoma is the most common solid tumor (cancer) to occur outside of the brain in children. 
Although high doses of chemotherapy followed by bone marrow transplantation can achieve a 
complete remission in a large percentage of patients, most (60%) of high risk patients will 
subsequently relapse and die of progressive disease. We wish to use a novel gene therapy 
approach to try to eradicate the relatively small number of cancer cells that survive maximal 
chemotherapy, or to treat progressive disease in patients that have failed therapy. To accomplish 
this we win “insert” genetic material (DNA) designed to express human gamma interferon (y- 
IFN), using a DNA delivery system known as a retroviral vector, into tumor cells obtained from 
the patient or cells from neuroblastoma patients with a shared tissue type (HLA type). We will 
then inject y-interferon producing neuroblastoma cells (y-IFN) in an effort to provoke an 
“immune” response against the cancer cells. The purpose of this study is to determine the 
maximal tolerated dose of such genetically engineered cells, and to obtain preliminary information 
regarding efficacy. Injection of y-IFN producing tumor cells has resulted in protective immunity 
against “non-engineered” parental tumor cells in some animal models. 
Tumor cell lines will be derived from clinical specimens, obtained at the time of surgical resection 
of tumor, from diagnostic bone marrow aspirations, or from peripheral blood. These tumor cell 
lines will be infected with a y-IFN producing retroviral vector prepared by Viagene Inc. (San 
Diego). Following this, we will select for “engineered” tumor using the antibiotic G418 (which 
kills cells that do not carry the vector) and measure levels of y-IF*N production. We will test for 
sterility of the engineered cells, and freeze them for storage until needed. Just prior to use, they 
wUl be thawed, irradiated (with X-rays) to make sure they cannot grown in the patient We wUl 
then inject various doses of tumor cells into the patient under the skin, according to a schedule 
outlined in the protocol, at 2 week intervals. We will determine whether this approach is safe, 
whether it increases the number of patients who remain disease free, whether it can decrease the 
size of tumor which is already present, and fmaUy, whether a specific immune response can be 
measured in the laboratory following vaccination with genetically engineered neuroblastoma cells. 
[ 88 ] 
Recombinant DNA Research, Volume 19 
