Recombinant DNA Advisory Committee - 09/9-10/93 
not will be interpretable. Dr. Parkman asked the investigators to summarize their earlier 
results from studies using the M24 cell with and without systemic IL-2 administration. 
Dr. Geiduschek asked whether the IL-2 producing M24 cells will be derived from a 
clonal cell line or mass cell culture transduced by the vector? Will the cell line be 
selected for high \Lr2 secretion? 
Ms. Meyers raised concerns in her written comments about the use of the term "vaccine" 
and the statement about the financial costs for patients participating in this trial. The 
Informed Consent document does not include a request for autopsy. Dr. Walters 
questioned if the first sentence of the Informed Consent document adequately states the 
purpose of the study. 
Investigator Response~Dr. Economou 
Dr. Economou explained that the present study combines the merit of two approaches of 
immunotherapy of cancer, i.e., transduction of an IL-2 expressing vector in patients' 
autologous tumor cells and an allogeneic cell line. Studies in animal models suggest that 
a "bystander effect" is produced by this immunization. Reduced tumorigenicity and 
enhanced immunogenicity is achieved by mixing untransduced tumor cells with 
immunologically irrelevant cytokine-producing cells. The local continuous production of 
cytokines by cells adjacent to autologous tumor cells is sufficient to provoke 
immunological responses to tumors. In regard to the rationale for selecting the M24 
melanoma cell line for transduction by the IL-2 vector, he explained that the IRB urged 
him to use M24 because it is a well characterized cell line that has been used extensively 
in previous clinical trials, and it appears to be safe for human use. 
Clarifying the question about the source of funding for the present study, Dr. Economou 
said that the present study will be funded by NIH through an implementation program 
project grant. Genetic Therapy, Inc., will provide scientific collaboration but no direct 
financial support. The IL-2 producing cell line will be made in the investigator's 
laboratory that is funded by NIH. 
Responding to a question about lack of direct data on M24 cells, Dr. Economou said 
that in preclinical studies the M14 cell line was used, and similar results were obtained 
with the M24 cell line although those data were not included in their published paper. 
Dr. Zallen said those relevant data should be presented in this proposal. Dr. Miller 
asked whether the investigators have already isolated a high IL-2 producing cell line. Dr. 
Economou responded that they have not isolated a high producer to date. The 
investigators are waiting for the biosafety testing requirements from FDA. As to the 
question of whether 5,000 rads irradiation is sufficient to inhibit cell proliferation. Dr. 
Economou said that 5,000 rads is the dose used for this cell line in other tumor vaccine 
studies at the University of California, Los Angeles. No tumor growth has ever been 
observed at the inoculation site in other clinical trials. Responding to Dr. Doi's question 
about possible adverse effects from repeated immunization with M24 cells, Dr. 
Economou said that no adverse immunological reaction has been observed in the last 10 
years of clinical trials with these cell lines. Dr. Economou agreed to perform HLA 
[210] 
Recombinant DNA Research, Volume 18 
I 
