Recombinant DNA Advisory Committee - 12/2-3/93 
data, this protocol is thought to be premature and not be recommended for approval. 
Dr. Parkman stated that scientific rationale for injection of untransduced cells was not 
well presented. This part of the protocol should be separated from the gene transfer 
protocol. Since the specificity of the CTL response has not been demonstrated, approval 
of the protocol is not justified. 
Review-Dr. Zallen 
Dr. Zallen questioned the scientific basis for treating HLA-A2 patients with a rotation of 
3 different cell lines. She expressed concern about the Informed Consent process. 
Approximately 38% of the subjects recruited onto this study will later be informed that 
they are ineligible to participate based on the results of the HLA typing. How will the 
investigators deal with the emotional disappointment expected in these individuals? The 
protocol includes the statement "the financial costs of treatment are borne by the 
Biological Response Modifiers Program (BRMP) of the National Cancer Institute". 
However, this statement is not included in the Informed Consent document. The 
Informed Consent document should be revised to include requests for autopsy and long- 
term follow-up. 
Other Comments 
Dr. Geiduschek asked about the dilution of vector sequences following cell expansion. 
Since the BPV vector is non-replicating, will the vector be present after expansion of the 
transfected cells in vitro ? Is the level of B7 expression stable in the clonal cell lines? 
Dr. Leventhal agreed with Dr. Zallen's concern that the Informed Consent document 
does not properly inform subjects that they may be ineligible to participate in the study if 
determined not to be HLA-A2 or HLA-A1. Dr. Leventhal said that the Informed 
Consent document is too assertive for a Phase I experimental study and is unclear about 
how patients will be assigned into the control and experimental groups. 
Dr. Carmen asked about Ms. Grossman's question about the incomplete vector sequence. 
A discussion ensued about the necessity to submit a complete sequence of every vector 
submitted for RAC review. Dr. Miller said that an assembled sequence is adequate for 
the current proposal. The investigators have demonstrated the functionality of the gene 
insert, the most important test for this construct. Since this gene construct is not 
proposed for a therapeutic purpose of correcting a gene deficiency, determination of the 
entire sequence of the gene insert is not essential. Insisting that the entire construct be 
sequenced would incur additional costs that are unnecessary. Dr. French Anderson of 
the University of Southern California noted that the Points to Consider require 
investigators to provide either a complete nucleotide sequence analysis or a detailed 
restriction enzyme map of the construct. There is no absolute requirement to totally 
sequence every gene construct. 
Investigator's Responses--Drs. Fenton and Sznol 
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Recombinant DNA Research, Volume 18 
