Recombinant DNA Advisory Committee - 2/10-11/92 
Dr. Mclvor moved that the review of this protocol be deferred to the HGTS since: (1) the 
procedure targets a different cell population, hematopoietic stem cells, which have not 
been extensively discussed or approved previously by the RAC, raising questions 
concerning the safety, efficacy, and proposed feasibility of the procedure; and (2) the 
amendment lacks specific responses to the Points to Consider in the Design and Submission 
of Protocols for the Transfer of Recombinant DNA into the Genome of Human Subjects. 
There was no second to Dr. Mclvor's motion and the discussion was directed to the 
primary reviewer, Dr. Post. 
Review~Dr. Post 
Dr. Post stated that the amendment extends well beyond a minor change that can be 
approved solely by the RAC's Chair. Not only is the vector being changed, but the target 
cells are different. Dr. Post summarized the revised protocol as involving treatment of 
patients with granulocyte colony-stimulating factor (G-CSF) and the harvesting by 
apheresis of CD34( + ) cells. There is published data with mice and unpublished data with 
humans that suggests that G-CSF will lead to mobilization of CD34( + ) cells into the 
peripheral circulation. These CD34( + ) cells would be transduced with a new retroviral 
vector containing a gene coding for ADA expression and reinfused into the patients. 
Dr. Post stated that the revised protocol would offer additional benefits. Transduction of 
progenitor cells might increase the survival of ADA expressing cells. The cells would have 
an opportunity to differentiate which would raise the patient's level of immunocompetence. 
Although these benefits would be reasonable expectations, there is no experimental data to 
support these conclusions. The information would be beneficial to the field of 
hematopoietic gene transplantation since this protocol would be the first example of 
marking transplanted CD34( + ) cells. Determining the duration and ability of these cells 
to differentiate into various cell lineages would be important information. The protocol 
seems to offer a potential for benefit with little additional risk since there would be 
continued transduction of T lymphocytes (the original protocol) along with the transduced 
CD34( + ) cells resulting in a dual therapy. 
Dr. Post questioned the extent to which CD34( + ) cells had already been transduced in the 
first two patients. The investigators responded that the culture conditions used when 
growing T lymphocytes did not include the growth factors, therefore, there was probably no 
growth of CD34( + ) cells. The investigators examined the second patient's cells following 
two weeks of culture, and no CD34( + ) cells were found. Also, no neomycin resistant 
colony-forming units (CFU-C) were found in peripheral blood from either patient, but 
polymerase chain reaction (PCR) analyses on granulocytes are still being performed to 
detect the vector. Dr. Post agreed that it is unlikely that CD34( + ) cells have been 
transduced. 
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Recombinant DNA Research, Volume 15 
