cells alone following bone marrow transplantation has resulted in recovery of both cellular and 
humoral immunity. 
There are several pieces of evidence that suggest that infusions of ADA gene-corrected 
autologous T cells could be of therapeutic benefit for these patients: 
1. Our experience with patients with metastatic cancer who have been treated with culture- 
expanded TIL has taught us that specific immune function (in this case anti-tumor 
immunity) can be greatly augmented by treating the patient with his own lymphocytes 
which have been expanded with IL2 in vitro. Therefore, in vitro expansion of cells may 
be more efficient than in vivo expansion in some cases. 
2. Polyclonal expansion of autologous T cell numbers in vivo by injections of IL2 has 
resulted in some therapeutic benefit in ADA(+)SCID patients. Polyclonal expansion in 
vitro could be expected to also be of benefit. 
3. The generally weak antigen specific responses seen in PEG-ADA treated patients suggests 
that these patients continue to have difficulty in maintaining clonal expansion of their 
antigen-primed lymphocyte populations in vivo. This may be a consequence of deficient 
intracellular concentrations of ADA. 
4. The in vitro survival of ADA(-) T cell lines is markedly enhanced if they have been 
genetically corrected by insertion of a functional ADA gene even though these cells are not 
exposed to elevated 2’deoxyadenosine concentrations in the extracellular medium. 
5. The observation that freshly obtained ADA{-)PBL transduced to express the hADA gene 
had a significant survival and functional advantage over non-transduced ADA(-) 
lymphocytes when transplantated into immunodeficient (but ADA normal) BNX mice 
strongly suggests that intracellular ADA provides significantly more reconstitution to 
the cells of the immune system of these patients than does extracellular enzyme alone. 
These observations suggest that patients treated with their own hADA gene transduced 
lymphocytes could experience immune augmentation which would surpass the partial 
immunologic reconstitution seen with PEG-ADA therapy alone. In addition, the ADA contained in 
the cells returned to the patient could serve as a cell-associated repository of ADA enzyme 
capable of detoxifying deoxyadenosine diffusing from extracellular sites. These observations 
serve as the rationale for the present clinical proposal. 
We therefore propose a two part clinical trial. Part 1 would study the effects of repeated 
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