July 30, 1990, Human Gene Therapy Subcommittee 
for efficacy was an attempt to get the maximum information possible from the study. 
Dr. Leventhal said she felt the study was inevitably a 
Phase I/Phase II study since no normal controls were being used in the study. However, 
she agreed with Dr. Miller that the major concern is that the patients are not subjected 
to a procedure that has no rationale. It is important to establish that the administered 
cells are working and that they are safe to use in the patients. She said she felt the 
Phase n component is implicit in the study by the patient eligibility criteria, but that the 
design is not strictly that of a Phase II study. 
Dr. Walters called on Dr. Claudio Bordignon to present the data from his experiments in 
Milan. Dr. Anderson voiced his appreciation that Dr. Bordignon had come from Italy to 
provide assistance in this review. 
Dr. Bordignon said that he was not a close collaborator in this study and that the 
experiments were not done with a view toward answering some of the questions raised 
during the review of the gene therapy protocol. He expressed concern over his ability to 
publish these data but said he had confidence in the fairness of the system. He noted 
that in his country, "a process like this would be unthinkable." He said he could simply 
go ahead and do gene therapy at any time without having the data reviewed. He noted 
that at this stage he did not feel he was ready to do a human gene therapy experiment. 
He also apologized for the limited information contained in the initial FAX, but noted 
that it was compiled quickly because he was traveling to Japan at the time. 
Dr. Bordignon prefaced his remarks about the experiments by stating that a specific 
limitation of the model is that he could not generate a primary or secondary response to 
tetanus toxoid antigens even when using a huge number of peripheral blood lymphocytes 
with a complete repertoire. It is beyond the capability of this model to address whether 
or not a primary response is obtainable to an antigen to which the patient has not been 
exposed. 
Dr. Bordignon said the model he used for the experiment was to take an immune 
deficient mouse (NIH-3 or BNX mouse) and reconstitute the mouse's immune system 
with human peripheral blood lymphocytes (PBLs). He said that his data confirm the 
survival and function of human T and B cells since human IgG can be identified in the 
peripheral blood of the mice after reconstitution. He then modified this model by using 
ADA-deficient human PBL which had been made ADA-positive by utilization of a vector 
and transduction and made immunocompetent by PEG-AD A. He looked for the 
presence of vector DNA, and thus vector-derived ADA, in the peripheral blood of the 
mice. 
Dr. Bordignon said that a single patient was used for all sets of the experiments, studying 
at most 2 mice per month, since only 20-30 million cells could be extracted from the 
Recombinant DNA Research, Volume 14 
[179] 
