HEPATOCELLULAR TRANSPLANTATION AND TARGETING GENETIC MARKERS TO HEPATIC CELLS 
1 
K. Clinical considerations in gene transfer in human subjects. i 
The efficacy and ethics of proposals for gene transfer in human subjects is 
dependent upon optimal patient management, including patient selection, informed 
consent, attention to psychosocial issues, and achieving adequate clinical follow-up. 
Much of the present protocol, and several additional proposals submitted in conjunction 
with this project, address clinical issues inherent in the application of somatic gene ] 
therapy : 
i) We believe the single most important clinical issue is the selection of 
patients in whom HCT will have clear therapeutic intent, and in whom the potential risks 
associated with the transplant procedure and the use of recombinant retroviruses is j' 
commensurate with the course and therapy of the underlying disease process. We have 
identified several patients over the past year who we believe would have been candidates | 
for this experimental therapeutic intervention (See memo October 31, 1990 - Fred li 
Ledley, M.D. to General Clinical Research Center (GCRC)). j! 
ji 
We do not presently have any quantifiable parameters for patient selection. The 
selection of patients for liver transplant in general remains a difficult and 
controversial problem, particular in pediatrics where there is considerable regenerative 
potential from hepatic injury (Whitington and Balistreri, 1991). The work of Malateck | 
et al identified variables which predicted the risk of heath in children with 
progressive liver disease (Malatack, et al 1987) . The prognosis also varies [i 
considerable with the specific diagnosis. Other studies have addressed the question of i 
when to transplant children with acute hepatic failure (Peleman et al, 1987; O'Grady, j 
1988; Emond, et al, 1989; Psacharopoulos et al , 1980). n 
ii 
In order to generate additional data describing the TCH patient population which may i 
be candidates for this protocol, their short-term and long-term prognosis, the v 
availability and prognosis of OLT and any alternative forms of therapy which may be i 
available. We have instituted a series of clinical research protocols involving all i 
patients referred for potential OLT. These protocols are designed to assess the course n 
of the patient's liver disease, the availability of transplantation, the clinical [, 
indicators of hepatic function, the metabolic capacity of small amounts of residual | 
hepatic tissue, and the impact of the patient's nutritional state on their course and 
prognosis. We believe these data will provide a firm clinical base for the efficacious 
application of this technology. (Ferry et al. Clinical Course and Management of Hepatic y 
Transplantation, protocol submitted) . ^ 
ii) The second most important clinical issue is the need for patient follow-up ^ 
after gene transfer. This issue is one area in which the present proposal differs from i 
the gene transfer experiments of Rosenberg et al (1990). We propose to employ gene 
transfer in conjunction with a clinical modality, HCT, which has the potential to ^ 
reverse the patient's disease and lead to long-term survival. The Rosenberg protocol ^ 
involved the introduction of recombinant genes into Tumor Infiltrating Lymphocytes (TIL ^ 
cells) which were then infused into patients with advanced malignancies. This surgical 
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Recombinant DNA Research, Volume 14 
