Recombinant DNA Advisory Committee - 2/10-11/92 
clones would persist; however, it is difficult to extrapolate from the CMV study whether 
these cells will persist as long. 
Dr. Krogstad asked Dr. Greenberg to briefly review the nature of the evidence that CD8 
cells control HTV in terms of how much of the data is extrapolated from other viruses and 
how much of it is actual in vivo experience with HTV. Dr. Greenberg replied that evidence 
can only be extrapolated from other viruses; it is not possible to provide definitive data in 
humans that the CD8 response is essential for HIV. However, there is a large amount of 
data from other viruses. As AIDS progresses and CD4(+) cells are depleted, CD8( + ) 
cells become dysfunctional. It is likely that there is a loss of in vivo antiviral activity. It is 
not possible to determine the importance until the responses are reconstituted. 
Committee motion 
Dr. Mclvor made the motion that the protocol be accepted; Dr. Haselkom seconded. Dr. 
Carmen requested that several changes be inserted into the consent form. There are 
changes in paragraph 3 under the heading, Background and Purpose (page 548, line 8 of 
the RAC notebook). The original text is changed to read as follows: 
"We will insert hereditary material (genes) into the lymphocytes to be used in 
immunotherapy. The process of genetically modifying the lymphocytes involves 
creating a special genetic or DNA package consisting of three component parts: (1) 
a portion of a mouse virus which will serve as the delivery system and which cannot 
reproduce itself; (2) a bacterial gene which will serve as a marker so we can locate 
the modified cells; and (3) a portion of the herpes simplex virus gene which we 
believe will perform important missions described below. We will deliver this 
package into the genetic material of the HIV-specific lymphocytes." 
On page 552 of the RAC notebook, the following changes were suggested: (1) on line 1, 
paragraph 2, the word "mouse" is to be inserted in front of the word "virus"; and (2) on 
line 8, paragraph 2, the word "bacterial" is to be inserted in front of the word "gene." 
Dr. Leventhal requested additional changes in the consent form under the heading of 
Potential Benefits (page 552 of the RAC notebook). The first two sentences would be 
deleted and the final paragraph would read as follows: 
"The HIV-specific lymphocytes are able to kill cells already infected with the virus 
and it is hoped they will provide additional antiviral effects to those observed with 
AZT. Adoptive immunotherapy is effective therapy for many viral diseases in 
animal models and might provide long lasting immunity to HIV. The gene transfer 
procedure will allow the investigators to tell where the cells that have been given 
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