Human Gene Therapy Subcommittee - 11/21-22/91 
Dr. Greenberg explained that HIV seropositive patients with accurate diagnosis are 
living longer than earlier patients. B cell lymphomas are being identified with 
significantly increased frequency. Particularly with the use of AZT therapy early, it is 
becoming evident that the only manifestation of HTV that is detected in seropositive 
patients is B cell lymphoma. Approximately one-third of AIDS patients present with 
lymphoma as their only manifestation of the disease. As a consequence of the increased 
diagnosis of lymphoma, allogeneic bone marrow transplantation alone is being pursued 
as a multicenter trial for HIV therapy. Bone marrow transplantation in this setting 
provides a 40% long-term survival rate. The problem with this therapy is that AZT is 
probably not completely effective in preventing the reinfection of the transplanted 
marrow cells by residual HTV. Select cell populations, such as epithelial cells, may not 
be ablated by current regimens. Treatment of the lymphoma does not guarantee 
ablation of HTV or that the ability of the virus to reinfect new cells will be blocked. The 
transfer of T cell clones into humans results in clearly documentable transfer of 
immunity that persists for at least 6 weeks; these cells can be recovered and exhibit virus 
specificity. Therefore, the transfer of HIV specific T cell clones into HIV seropositive 
patients should provide an antiviral effect. 
In response to Ms. Meyers' concerns regarding payment, Dr. Greenberg said that third 
party carriers, insurance companies, routinely compensate for bone marrow 
transplantations for the treatment of lymphoma. Therefore, patients will be billed for 
the transplantation procedure. However, patients will not be billed for the T cell therapy 
designed to treat HIV. 
Dr. Greenberg responded to Dr. Epstein's question about whether the protocol would be 
initiated without the addition of the marker gene. He stated that HyTK is not merely a 
marker gene; it provides a clear function. That is, in the event that toxicity results from 
the administration of the T cells clones, ablation of these cells is readily achieved. 
Therefore, gene insertion is not separate from the T cell administration aspects of the 
protocol. Dr. Greenberg noted data from in vivo CMV T cell clones suggesting that 
there is no evidence of T cell toxicity in patients. CMV patients received 10 9 T cell 
clone cells on an outpatient basis. Oxygen saturation was measured, and there was no 
evidence of cell sticking to vessel walls as observed with TILs. In contrast to T cell 
clones, TILs are non-specifically activated lymphocytes that are generated in 
extraordinary non-pharmacologic doses of IL-2. The lethal problems that could be 
particular to HIV are central nervous system (CNS) toxicity, marrow suppression, and 
lymphocytic alveolitis, for which the potential to ablate the clones represents an 
important safety factor. 
In response to the clinical question regarding CMV infection following bone marrow 
transplantation. Dr. Greenberg stated that in the event that CMV viremia develops, 
ganciclovir therapy will be administered. If the T cell clones have already been 
Recombinant DNA Research, Volume 15 
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