Recombinant DNA Advisory Committee - 09/14-15/92 
lymphocytes from the identical twin of an human immunodeficiency virus (HIV) positive 
( + ) patient. The lymphocytes will be separated into CD4( + ) and CD8( + ) 
subpopulations. Each of these subpopulations will be marked with one of two different 
retroviral vectors, GINa or LNL6, and reinfused into the HIV infected twin. 
Transfection of the lymphocytes with the retroviral markers will determine survival of the 
infused cells. In addition, the investigators will examine any potential benefit resulting 
from the infusion of uninfected T lymphocytes. 
Dr. Post inquired whether there is any real expectation that this protocol will provide any 
therapeutic effect. The infusion of activated T cells into HIV( + ) patients may present 
an inherent safety issue because CD4( + ) cells are the target of HIV replication. Since 
these patients are already immunodeficient, infusion of activated T cells may increase the 
pathogenicity of the disease. The investigators responded to these concerns stating that 
there is a clinical protocol already in progress in which patients have received CD8( + ) 
cells and no untoward effects have been observed. However, these results do not predict 
the outcome of infusing large numbers of CD4( + ) cells. Language has been 
incorporated into the informed consent document informing patients that if untoward 
effects are observed as a result of the T cell administration, the protocol will be 
terminated immediately. In addition, patients will be monitored for viral titers. 
Dr. Post explained that the protocol presents a great deal of latitude with regard to the 
number of cells that will be infused. Peripheral blood mononuclear cells will be 
fractionated by CD4( + ) selection and/or CD8(-) depletion. Patients will receive 
between 3 x 10 9 and 2 x 10 11 fractionated cells. 
Although the investigators propose to use the standard retroviral vectors, GINa and 
LNL6, that have been reviewed numerous times by the RAC, it is unclear what assays 
will be performed to detect helper virus contamination. At the last RAC meeting, Dr. 
Anderson stated that the acceptable standard is currently to propagate the packaging cell 
line for two to three weeks after the vector has been harvested to demonstrate the lack 
of helper virus. Dr. Post stated that the Food and Drug Administration (FDA) has been 
conducting discussions regarding revised standards for monitoring helper virus. When he 
addressed concerns regarding vector safety testing, the investigators noted that the 
supplier of the vector, Genetic Therapy, Inc. (GTI), currently performs extended 
culturing of the packaging line following harvest as well as co-cultivation with an 
indicator cell line. It should be noted; however, that co-cultivation has not been 
accepted yet as a validated protocol for the detection of replication competent helper 
virus. He asked the investigators and Dr. D. Miller to respond to the importance of co- 
cultivation experiments. 
There are no restrictions on the patient's stage of disease as an inclusion or exclusion 
criterion for this protocol; patients can have an asymptomatic HIV diagnosis or advanced 
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Recombinant DNA Research, Volume 16 
