Recombinant DMA Advisory Committee - 3/3-4/94 
Other Comments 
Dr. Motulsky asked for additional information regarding the 65 discordant identical twins 
identified as eligible for this study. This patient population is a valuable resource for 
other genetic studies. Dr. Parkman inquired about the types and levels of cytokines that 
are released when the transduced T cells are activated by HIV. Will these cytokines 
cause adverse effects, e.g., edema, in anatomically defined areas such as the brain? If 
such a side effect occurs, is therapy available that would alleviate such effects? Is there 
data demonstrating that steroids cause apoptosis of these clones? 
Dr. Zallen inquired whether participation in this study will preclude the 65 discordant 
twins from participation in future protocols. She recommended that the Informed 
Consent document be revised to include a statement about long-term follow-up, even if 
subjects who have received transduced cells terminate their participation in the protocol 
prematurely. Dr. Hirano asked whether the Phase II portion of this study implies that 
efficacy is an endpoint. 
Dr. Walters called on Ms. Gracia Buffleben of Breast Cancer Action and ACT 
UP/Golden Gate, to read the written statement submitted by Mr. G'dali Braverman, 
ACT UP/Golden Gate. Mr. Braverman applauded Cell Genesys (sponsor) for seeking 
comments on this study from the HIV( + ) community. Mr. Braverman's comments 
focused on scientific issues of the protocol as well as the Informed Consent document. 
Mr. Braverman suggested the following: (1) potential participants should be informed 
that participation in this study may exclude their eligibility for other studies, (2) subjects 
in the control group should be allowed to receive the same treatment as the 
experimental group once the safety issues have been established, (3) the transduced T 
cell infectivity experiments should be expanded to include other HIV clinical isolates, (4) 
lymph node biopsy should be performed, (5) patient eligibility should include females, 
(6) is the viability of transduced cells affected by freezing and thawing? and (7) patient 
eligibility should be reduced from 18 to 13 years of age and localized treatment of 
Kaposi sarcoma should be permitted. 
Investigators' Responses-Drs. Walker, Lane, Zsebo, and Roberts 
In response to Dr. Carmen's comments about the description of the vector. Dr. Walker 
agreed to revise these sections of the protocol and the three Informed Consent 
documents in language that is understandable to laypersons. In response to Dr. 
Motulsky's question regarding discordant twins. Dr. Walker answered that approximately 
10% of the 146 (not 65 as stated earlier) pairs of discordant identical twins enlisted over 
the last 10 years are female. 
Dr. Walker explained that this Phase I/II study is divided into two treatment periods. 
The first period involves a single infusion of gene modified cells in the experimental 
group and nonmodified cells in the comparative group. After characterization of 
toxicides, the second treatment period will involve repeated infusions every 8 weeks for 
one year. Toxicity, immunological activity, and additional information with regard to 
Recombinant DNA Research, Volume 19 
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