Recombinant DNA Advisory Committee - 06/1-2/92 
antigens. Ninety-nine percent of patients receiving injections of SK-MEL-29 generated 
an allogeneic response, and no control patients demonstrated a response against these 
melanocyte differentiation antigens. If patients participating in this protocol generate 
responses to the melanocyte differentiation antigens, significant information will be 
obtained. It is known that to generate high affinity IgG responses, CD4 is necessary. 
Could this elicit an immune response against normal melanocytes? Responses against 
normal cells have never been observed in any of the animal models. Some of the 
murine models have remained healthy up to 9 months. 
Dr. Gansbacher stated that at the time he submitted the original protocol, no data was 
available regarding the capacity of the melanoma cells to secrete IL-2 following 
irradiation. He provided an update on the experiments that have now been completed. 
All of the various cell lines that have been assayed continue to secrete IL-2 for several 
weeks. The cell lines exhibit different levels of radiosensitivity, demonstrating varying 
survival times. 
In response to Dr. Kelley's concerns regarding the exclusion of patients who have 
previously received autologous or allogeneic tumor vaccines, Dr. Gansbacher stated that 
there were no instances of anaphylaxis in any of these patients. Therefore, there is no 
obvious need to exclude them. 
Dr. Gansbacher noted that he has included a section in the revised informed consent 
document that details long-term follow up for patients participating in the protocol. 
In response to Dr. Leventhal's comments, Dr. Gansbacher stated that patients will be 
monitored for systemic toxicity with IL-2. Patients will also be monitored for non- 
peripheral integration of retrovirus. Since these patients will receive lethally irradiated 
cells subcutaneously, there should be no viral spread to other areas. 
Dr. D. Miller reviewed the sequence of the NAPAD-IL2 retroviral vector. There is 
concern that the MoMuLV GAG region of the vector could produce a truncated protein. 
However, this response should not present a problem for this particular protocol because 
the investigators are trying to stimulate an immune response. 
Dr. D. Miller inquired if assays will be performed to observe the production of 
endogenous human helper virus following irradiation? Dr. Gansbacher stated that these 
safety studies have been performed. NIH 3T3 and HeLa cell amplifications were 
performed, and there was no evidence of helper virus production. Dr. Gansbacher said 
that he has also searched for G418 resistant colonies and performed reverse transcriptase 
assays. 
In response to Ms. Meyers comments regarding patient eligibility requirements, Dr. 
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Recombinant DNA Research, Volume 15 
