Recombinant DNA Advisory Committee - 06/1-2/92 
Freedom of Information Act. 
Dr. Gilboa asked the RAC if the investigators could give an oral presentation of the data 
contained within the manuscript during today's meeting? Dr. Post responded that there 
would be a substantial amount of data to review, and that an oral presentation would not 
cover this information adequately. The committee members need time to examine this 
data. Dr. Parkman reiterated his comments regarding submission of the data. The 
manuscript data should have been included in the submitted materials. There should not 
be a problem if data tables appear in the protocol submission and appear at a later time 
in a published manuscript. 
Dr. Haselkom noted that the investigators submitted a very ambitious and interesting 
proposal to apply molecular biological studies on HIV replication to a proposed long- 
range therapy designed to interfere with the progression of HIV infection to full blown 
acquired immune deficiency syndrome. CD4( + ) PBL would be obtained from HIV( + ) 
patients. These PBL would then be transduced with a murine retroviral vector that 
expresses a 60 nucleotide RNA molecule called TAR. TAR mimics an RNA sequence 
of HIV which binds to a protein called TAT. The interaction between the TAT protein 
and the TAR RNA is crucial for the replication of HIV. 
Dr. Haselkom described the 21 day in vitro experiments in which a retroviral vector 
expressing the TAR RNA, effectively reduced HIV replication in PBL. However, he 
noted that critical experiments have not been performed on PBL of HIV( + ) patients. 
Dr. Haselkom noted that the investigators forwarded a copy of the preprint to him. 
Since this manuscript was not available for distribution to the other committee members, 
Dr. Haselkom summarized one of the critical experiments. He described an in vitro 
experiment in which PBL were obtained from healthy individuals, stimulated with IL-2 
and phytohemagglutinin (PHA), and cocultivated with vector producing cells. Four days 
post stimulation and exposure to the vector, the PBL were challenged with HIV for 21 
days. The investigators report a 90-95% inhibition in HIV infection over this 21 day 
period. If the fraction of PBL being transduced is approximately 10-20%, then a very 
significant bystander effect is occurring. These data would indicate that there is 
protection of the untransduced neighboring cells. There needs to be an elaboration on 
this bystander effect. 
Dr. Haselkom stated that the data contained within the preprint is different from the 
experiments being proposed in humans. The human protocol involves the collection of 
PBL from HIV( + ) patients by aphereAs. These PBL will not be stimulated with IL-2 or 
PHA, but will be incubated with retroviral supernatants. These transduced PBL will 
then be reinfused into the patient. Persistence of the transduced PBL will be monitored 
by competitive PCR. These assays have not been described in detail in the protocol. 
[690] 
Recombinant DNA Research, Volume 15 
