June 1, 1990, Human Gene Therapy Subconmittee Minutes 
be addressed by the investigators. 
Dr. Anderson said there were no commercial concerns. Genetic Therapy, Inc. is a 
company which is performing official business of the United States Government under a 
CRADA agreement from the National Heart, Lung, and Blood Institute. 
Dr. Walters noted that Dr. Mulligan regretted not being in attendance and asked if 
everyone had read his letter. Dr, Walters asked whether the issue raised in the latter 
portion of the first paragraph of Dr. Mulligan's letter was a concern to any of the 
subcommittee members. 
Dr. Neiman addressed the issue which Dr. Mulligan raised. If one infuses an expanded 
population of cells with a distorted ratio of functional subgroups into an individual, and 
if such cells persist, it might be possible to create a situation in which the patient's 
immune system would be further compromised. This was considered as a purely 
theoretical issue and he was not sure about the background for the statement or whether 
there were models to suggest that this could occur. 
Dr. Parkman replied that there clearly are cells which respond in an auto-reactive 
manner and cells which regulate such occurrences. The ratio of these cells is very 
important but it is a biological phenomenon with a phenotype that cannot be predicted. 
He added a significant concern is the potential for producing some sort of autoimmune 
disease, rather than a decrease in the minimal endogenous immune reactivity. 
Dr, Walters summarized the questions being put forward. The questions were arrayed in 
four major areas: 
1. Who are the patients? The selection criteria, inclusion and exclusion criteria, 
should make the distinction between stable and non-stable or debilitated patients. 
2. Is it safe? Should animal models of oncogenesis be used? Will intraperitoneal 
infusion be used as opposed to intravenous infusion? What are the amounts of 
blood to be drawn from patients? 
3. Is the protocol likely to be effective, and if so how will we know it is effective? 
What are the clear outcome variables in terms of both clinical and biological 
variables? What are the differences in co-cultivation techniques between those 
being used in Italy and those being used by the investigators in Bethesda? What 
is the biological justification for ex vivo host selection as opposed to inserting the 
cells in short-term culture and giving non-selected cells? W^at is the need to go 
through an additional step of selection before the cells are given? What are the 
quantitative measures of survival of the lymphocytes? 
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Recombinant DNA Research, Volume 14 
