Recombinant DNA Advisory Committee - 09/14-15/92 
Review— Dr. Walters 
Dr. Walters asked the investigators to hypothesize about the fate of the gene marked 
cells if they survive and contribute to reconstitution. The investigators propose to use 
the LN retroviral vector. How does LN compare to the LNL6 vector that has already 
been approved for use in other human gene therapy protocols? How many animals have 
been studied in the in vivo experiments to date? What is the transduction efficiency of 
human cells by the proposed retroviral vector? With regard to the informed consent 
document, Dr. Walters stated that it was clear and targeted directly to the gene marking 
aspect of the protocol. 
Other Comments 
Dr. Parkman said that the RAC needs to define its criteria for a vector, regardless of the 
supplier of the vector. A set of vector standards needs to be established. These 
standards may evolve as assays are refined, and their level of sensitivity is increased. 
Since the safety standards established by the RAC will continue to evolve, it is critical 
that the RAC maintain consistency, fairness, and objectivity in its review. If Dr. 
Schuening already has vector supernatants that meet the same safety standards as were 
required for Drs. Walker and Blaese, then they should be allowed to use the 
preparations that already exist. Have Dr. Schuening's preparations already been 
approved by the FDA? If Dr. Schuening's vector is not analogous to the vector proposed 
in the protocol review this morning, would the new extended S + /L‘ assay standard be 
appropriate? 
In response to Dr. Parkman's comment, Dr. Geiduschek stated that the issue of equity 
between commercial enterprises is not the dominant one. The question is how to assure 
safety within agreed guidelines. Dr. Parkman responded that the S + /L* assay has been 
the gold standard for the RAC up to this point. GTI has provided numerous lots of 
vector supernatants screened by this assay method. The issue is whether the RAC 
should use a different standard for safety between two protocols reviewed at the same 
meeting; this issue is about fairness. The fact that a better assay exists should not 
influence the review of this protocol. If the RAC decides that the extended S + /L' assay 
is now the standard, then that should be a requirement for protocols presented at future 
RAC meetings. Dr. Geiduschek added that Dr. Schuening is using a vector and supplier 
different from those used in the Walker-Blaese protocol. 
Dr. Zallen said that the informed consent document states that the gene marking 
protocol will not directly benefit the patient; however, the patient will be responsible for 
the cost of the therapy. First, the gene marking protocol is not considered therapeutic. 
Second, Dr. Schuening agreed that the statement about payment by the patient would be 
removed. She asked the investigators to respond to these discrepencies in the informed 
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