Recombinant DNA Advisory Committee - 09/9-10/93 
protocol. The motion passed by a vote of 17 in favor, 0 opposed, and no abstentions. 
VI. MAJOR AMENDMENT TO APPENDIX D-XXVII OF THE NIH GUIDELINES 
REGARDING A HUMAN GENE TRANSFER PROTOCOL ENTITLED: PHASE I 
STUDY TO EVALUATE THE SAFETY OF CELLULAR ADOPTIVE 
IMMUNOTHERAPY USING GENETICALLY MODIFIED CD8(+) HIV-SPECIFIC T 
CELLS IN HIV SEROPOSITIVE INDIVIDUALS /DRS. GREENBERG AND RIDDELL 
Review-Dr. Straus 
Dr. Walters noted that Dr. Miller will abstain from discussion and voting on this protocol 
due to a conflict of interest (employed by the same institution). Dr. Walters called on 
Dr. Straus to present his primary review of the request for a major amendment to the 
human gene transfer protocol submitted by Drs. Phillip Greenberg of the University of 
Washington and Stanley R. Riddell of the Fred Hutchinson Cancer Research Center, 
Seattle, Washington. This protocol represents a modification of a previously approved 
Phase I study to evaluate the safety of adoptive immunotherapy of autologous 
genetically-modified CD8( + ) HIV-specific T cell clones in HIV infected individuals with 
lymphoma following bone marrow transplantation (BMT). Apparently, the accrual from 
that study has been slower than expected; but the preliminary data suggest that 
competent cells can be detected in the recipients. The present modification will allow 
the investigators to accrue HIV-seropositive individuals who lack opportunistic infections, 
have CD4 cell counts between 200 and 500, do not have lymphoma, and who are not 
undergoing BMT. 
As in the previously approved protocol, the patient's T cells will be modified by a 
retrovirus containing a hybrid insert of the hygromycin resistance (Hy R ) gene for marking 
as well as the herpes simplex virus thymidine kinase (HSV-tk) gene. The HSV-tk suicide 
gene will provide a safety feature that allows the transduced cells to be eliminated with 
the antiviral drug, ganciclovir, if adverse effects are encountered. This latter concept will 
be tested in a group of 3 patients enrolled in this study. Dr. Straus stated that this 
protocol is well developed with the vector and the strategy thoroughly described. He 
recommended approval of this modification. 
Review-Dr. Leventhal (presented by Dr. Straus) 
Dr. Leventhal's written comments raised several questions that have been adequately 
addressed by the investigators. The investigators accepted her suggestion that ganciclovir 
should be administered in the hospital for the first two days in the event that the 
treatment exhibits an unanticipated toxic effect. She asked about the necessity for lymph 
node biopsies prior to treatment. The procedures described for assessing neurologic and 
pulmonary toxicity are inadequate and more extensive evaluations should be performed. 
Any adverse effects, if encountered, should be reported to the RAC as well as the IRB. 
She questioned the future plans for evaluation of this technique. How will the 
investigators proceed if they find that the treatment is neither toxic nor effective? She 
noted that her comments were minor, and she recommended approval of this major 
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Recombinant DNA Research, Volume 18 
