Non Technical Description 
Non-Technical Abstract 
Cancer of the ovary is responsible for more than 12.000 deaths annually in the United 
States. The disease is usually only diagnosed at a stage when the tumor has spread to involve 
structures in the abdominal cavity. The standard treatment for ovarian cancer involves surgical 
removal of the larger tumor masses combined with a combination of chemotherapy drugs. 
Although new chemotherapy drugs such as taxol are effective, complete responses are few. and 
toxicity is high. It therefore remains necessary to develop new treatment strategies to improve the 
survival and quality of life of patients who are afflicted with ovarian cancer. 
The results of studies conducted in our laboratories and others have shown that a 
particular cell type called the tumor infiltrating lymphocyte (TIL) can be isolated from the 
cancerous tumors that involve the lining of the abdominal cavity and the surface of the intestines. 
When these cells are removed from the body and are grown together with the patients tumor cells 
in tissue culture, along with a drug called recombinant interleukin-2 (rIL-2), the TILs will 
frequently increase to larger numbers and develop an increased capacity to kill tumor cells 
obtained from the patient. rIL-2 is a protein substance that is almost identical to a natural 
substance that is found in the body and is produced in very small amounts by the cells of the 
body’s immune system called lymphocytes. We are currently growing large numbers of TILs for 
the experimental treatment of patients with advanced ovarian cancer in a clinical trial. This type 
of treatment has been called adoptive cellular immunotherapy. In this trial we purify a particular 
type of TIL called “CD8+ TIL” which appear to be responsible for the killing of tumor cells in tissue 
culture in certain cases. 
This gene marker protocol will address an important scientific question: whether ovarian 
TIL-derived T cells that are expanded ex vivo in rIL-2 for intraperitoneal injection, concentrate 
within metastatic tumors of the abdominal cavity. This information will be helpful in the 
development of improved therapies for ovarian cancer. In the past this type of question could 
only be addressed by placing a radioactive label onto the cells and trying to trace the cells using a 
gamma camera held over the patient. These techniques remain in use but are not sensitive or 
specific enough to address the questions that are being posed. 
Recently, use has been made of defective mouse viruses that have been genetically altered 
in the laboratory so that they are rendered incapable of multiplying in the patient. These viruses 
have been used to transfer new genetic information into cells. The gene transfer approach is 
being used to introduce a stable marker into cells that are being returned to the body for marker 
studies or in the development of new therapy approaches. Appropriate concerns have been 
expressed regarding utilization of these defective viruses in patients. Marked improvements in 
design and in quality control are contributing nevertheless, to safer and more efficient clinical 
applications. 
In our study we intend to use the defective virus GlNa, to transfer the gene for marker 
DNA. This marker gene is not present in human or mammalian cells. The gene encodes for an 
enzyme called neomycin phosphate transferase (NPT). The defective virus and related forms have 
been used on a number of occasions to treat patients without reports of toxicity. 
Patients who are enrolled in a study to be treated with TIL will be eligible for the marking 
protocol. During the growth of TIL in culture a bacterial “marker” gene will be inserted into a 
portion of cultured TIL cells using a defective mouse retrovirus so that they can be traced after 
reinjection Into the patient. Following injections of a mixture of gene marked and unmarked 
cells, samples of blood (about 10 cc each) and peritoneal fluid (approximately 100 cc) will be 
obtained on days 4. 11. 18 and at one month after receiving the TIL injection. One month after 
receiving the TIL. patient’s will undergo a laparoscopy to evaluate their responses to the 
treatment. At this time biopsies will be obtained from tissues suspected of harboring cancer. 
Biopsies will also be obtained from certain normal tissues, e.g.. peritoneum (lining of abdominal 
cavity) and lymph node (if easily accessible). These biopsies will be obtained to determine if the 
TIL have migrated Into the tumor. This information might be useful for the development of future 
treatment strategies in other patients with ovarian cancer. The laparoscopic surgery will be 
performed to evaluate the response to the treatment and not for the marker study alone. Nine 
patients may receive the retrovirus modified cells. 
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Recombinant DNA Research, Volume 19 
