June 1, 1990, Human Gene Therapy Subcommittee Minutes 
previously mentioned, out to beyond 500 days. Dr. Kelley said this did not answer the 
question as to the half-life in the absence of 11^2. It appeared from what Dr. Blaese had 
said, that the half-life was then in the region of 4-5 days. Dr. Blaese replied that the 
only way to really determine the efficacy of the treatment was to do the protocol. 
Dr. Blaese said that the protocol contains a very extensive immunological evaluation 
comparing the patient after treatment to baseline, to determine whether the patient has 
been improved by the therapy. He said they would do standard tests such as mitogen 
proliferation, skin tests, and cloning out cells trying to assess whether they have the gene 
in them. Attempts will be made to get antigen cloning to work in this population. He 
added that they will immunize patients early on with non-reactogenic viral vaccines. 
Then they will look in vitro to see if there are memory cells in the peripheral blood of 
the patients which would boost antibody responses to these viruses. 
Dr. Blaese said the differences between the Italian protocol and this one were trivial in 
that the Italians were using PHA to stimulate the cells whereas they were using a 
monoclonal antibody directed against the T cell receptor. He added that Dr. Bordignon 
is using a different vector, but that the LASN vector has been examined and has 
equivalent levels of expression. It is planned for use unless a better vector comes along 
in the meantime. 
As for disclosures to the families. Dr. Blaese said he and Dr. Culver had met with three 
families to discuss the details of the patients' clinical courses and to explain the protocol 
in general. He said they specifically mentioned problems of insertional mutagenesis, the 
possibility of inducing an autoimmune process by giving lymphocytes, and the unknown 
effects of these cell infusions in children. Further, they discussed the problem of the 
press possibly establishing the identity of the patients. If this occurs, they may have more 
press exposure than they want. 
There is a biological justification for selection. It is essential to select the cells if they 
are to start escalating doses. He said the efficiency of the process is averaging 10-20 
percent. He did not want to have to expose patients to five times more cells than 
necessary. If selection could not be done, then the dose would not be escalated. 
In response to a question by Dr. Parkman as to what was the minimum acceptable 
weight for apheresis. Dr. Blaese said this would be done by hand and not by machine. 
The machine procedure was included in the protocol give a general idea of the 
consequences of apheresis and the potential side effects. Dr. Leventhal asked about 
using peripheral IV for apheresis. Dr. Blaese responded that the youngest candidate has 
a peripheral line inserted, while the other children are older and have good peripheral 
veins at this point. He pointed out that they would use a Brovia or Hickman catheter 
for this purpose. 
Recombinant DNA Research, Volume 14 
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