potentially allowing multiple ABMT from a single marrow harvest (see 1.2 
above). 
4.0 STUDY OUTLINE AND SAFETY 
This study proposes to transduce marker genes into aliquots of marrow obtained for 
ABMT in patients in remission of AML. 
The vector to be used in the transduction studies is the helper free LNL6 retrovirus, 
which has been extensively studied in rodent models and in non-human-primates and 
which was approved for use in man in 1989. The results of the first in vivo human 
study on transduced marrow derived cells have been reported at The American 
Society for Clinical Oncology and in the New England Journal of Medicine. The 
safety data required for the granting of the IND (#3042) under which this first study 
took place are contained in the four volume directories made available to the 
Chairman of the IRB. The current proposal will cross reference these data. The 
major safety concerns and their resolution are also summarized in a review by 
Cometta et al (submitted to the committee) a precis of which follows. 
4.1 The LNL-6 Vector 
The LNL-6 vector (Figure 1) was developed in the laboratory of A. Dusty 
Miller and is a safety-modified version of the retroviral vector N2. The vector 
was constructed by modifying the Moloney murine leukemia virus (MoMLV) 
by removing the viral genes and replacing them with the bacterial neo^ gene. 
The vector has a number of modifications to decrease the likelihood of 
successful recombination between the vector and packaging cell genome that 
might result in replication-competent virus. The modifications include deletion 
of 5’ and 3’ sequences to minimize homology and substitution of a stop codon 
at the gag start codon. 
4.2 The LNL-6 Producer Cell Line 
The LNL-6 producer cell line was created by transfection of the LNL-6 vector 
into the PA317 producer cell line. The viral containing supemate obtained 
from the LNL-6 producer cell line was extensively tested for exogenous 
pathogens and replication-competent virus. 
The supernatant (provided by Genetic Therapy, Inc.) to be used for human 
clinical use has passed all studies for contaminating microorganisms, and no 
pathogens were detected. The supernatant is approved for clinical use by the 
U.S. Food and Drug Administration. 
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