Recombinant DNA Advisory Committee - 09/9-10/93 
the RAC with information about the source of the proposed cell line. In conclusion, the 
study may demonstrate the potential to reduce human tumor growth, and there do not 
appear to be any new problems associated with the gene transfer portion of the proposal. 
Review-Dr. Doi 
Dr. Doi stated that the investigators have responded to most of his initial concerns; 
however, he noted that the use of the term "vaccine" in the title, throughout the protocol, 
and in the Informed Consent documents is misleading to patients and others. The 
proposed material to be used in the treatment is not a "vaccine" in the classical sense. 
The investigators should respond to the following questions: (1) How many transduced 
M24 cells are required to produce between 10 3 and 10 s picograms of IL-2? (2) Are 
transduced cells stable during cryopreservation? (3) Will patients react immunologically 
to the allogeneic melanoma cell line after biweekly and monthly injections over a period 
of one year? Dr. Doi said that the overall experimental design appears to be based on 
sound and reasonable procedures, the study is straightforward, and the endpoints are 
well defined. Dr. Doi recommended approval of the protocol. 
Review-Dr. Zallen 
Dr. Zallen explained that her questions are directed to three areas. In regard to the 
animal and preclinical studies, most of the preclinical studies were performed with a 
different melanoma cell line, M14. Very little data was submitted using the M24 cell 
line that will be used for the clinical trial. The relevant animal studies described in a 
preprint have not been included as part of the proposal. The expected bystander effect 
has not been defined in the animal studies. In the area of experimental design and 
patient selection, HLA typing should be performed prospectively to confirm that there is 
a match with the M24 cell line before patients are enrolled onto the study. In most 
preclinical studies, cells were irradiated with 10,000 rads, yet 5,000 rads is proposed for 
the clinical study. Is 5,000 rads a sufficient dose to lethally irradiate the M24 cells? 
In regard to the Informed Consent process, Dr. Zallen asked the investigators to 
elaborate on how patient consent will be obtained. Several specific changes were 
suggested to the Informed Consent document: (1) the use of the term "vaccine" is 
misleading to the patients, (2) it is unclear as to the number of biopsies that will be 
performed and the associated risks, (3) the section that describes financial risks to 
patients that could result from research-related injuries should be clarified, and (4) an 
exaggerated number of $100,000 was originally assessed as the patient's upper limit of 
financial costs. That figure should be removed from the Informed Consent document. 
Other Comments 
Dr. Smith asked whether there are data demonstrating that 5,000 rads is sufficient to 
lethally irradiate the M24 cells. Dr. Parkman said that HLA typing of patients will 
facilitate interpretation of research results because differences in patient responses 
between those who share HLA antigens with the M24 melanoma cell and those who do 
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