Recombinant DNA Advisory Committee - IjAftX 
any way of testing this that would be relevant. By using a retroviral vector there will be 
no way of controlling the location of gene insertion and therefore genes could be 
activated or inactivated at any position in the genome. 
Dr. Carmen said his review was more from a layman's standpoint, since his background 
was in social science, and that he would split the review into issues of assessment of the 
research design and informed consent. He agreed that the protocol was very similar to 
the Anderson-Blaese-Rosenberg protocol involving the Neo’^-marked TlLs, but that he 
was confused by the fact that there were 5 mini-protocols under the umbrella of this 
overarching protocol that involved patients suffering from cancers other than melanoma. 
Furthermore, that in response to a question from Dr. Parkman, Dr. Lotze had replied 
that. 
"The main goal of our series of protocols is to evaluate the ability of 
combinations of IL-2 and IL-4 to enhance the antitumor efficacy of the 
adoptive transferred TILs." 
Dr. Carmen said that this sounded more like a Phase II trial than a Phase I trial. 
Therefore, it seemed that a risk-benefit assessment must be performed and he went 
about it in the following two steps: 
a. Assessment of the TIL cell expansion, in vitro, in the presence of both IL-2 
and IL-4, followed by an application of retrovirally mediated genetic 
transduction to a small portion of the TILs; and, 
b. Assessment of the introduction, in vivo, of the mutant artifacts in 
conjunction with IL-2 and IL-4. 
Dr. Carmen said that after using this assessment technique he thought that, judged solely 
as a gene transfer exercise, the protocol seemed reasonable and appropriate, using the 
Anderson-Blaese-Rosenberg regimen, to track the lymphocytes being used. As a TILs 
cell therapy exercise, the benefits to the patients were speculative, but the risks to the 
patients, given their terminal status, were minimal. 
Dr. Carmen said that when the Anderson-Blaese-Rosenberg protocol to treat patients 
with severe combined immune deficiency (SCID) patients was before the RAC, he had 
asked the investigators to include in their informed consent documents disclosures which 
would identify the contents and purposes of all alien DNA employed as recombinants 
which the investigators agreed to supply. In the protocol before the committee, nothing 
is included which tells the patient either what the gene is that is being employed or 
information about the retroviral vector. He identified this as the only deficiency in the 
informed consent document. 
Recombinant DNA Research, Volume 14 
[461] 
