tors in conjunction with the Institutional Biosafety Officers will be used to 
educate all health care workers as to the protocol and relevant hazards, pre- 
cautions and procedures. 
9.4 Environment. After receiving the AdcvCFTR.lO treatment, the risk to the 
environment while the patient is an inpatient will be negligible, based on the 
considerations described above. The risk to the environment after discharge is 
limited to the possibility that the individual will become infected with a 
virus that will either complement or recombine with the vector DNA still pres- 
ent in this individual. From the data available, this is very unlikely, but 
cannot be proven impossible without carrying out the human trial. If com- 
plementation were to occur, the risk to the environment might be small amounts 
of Ad^vCFTR.10 released. Since AdcvCFTR.10 is replication deficient, this will 
have limited spread. If an individual (other than the original patient) were 
to be exposed, in the context that animal studies show no risk from the ex- 
ogenous gene (the CFTR cDNA) , there should be no risk, particularly in the 
context that shedding will be associated with far less amounts of the vector 
that will be administrated to the study individuals. If recombination were to 
occur, the most likely possibility is that it would occur from a crossover 
between the left end of the new infecting virus (providing the missing El 
functions) and the right end of the vector i.e., (this would produce a repli- 
cation competent E3‘ Ad5) . This should be no different, and likely less viru- 
lent, than a replication competent E3* adenovirus. This concept is supported 
by a human trial with oral administration of a replication competent E3' re- 
combinant hepatitis adenovirus vaccine. In the event that the vector continues 
to be shed from the study individual following administration, or the vector 
recombines with another virus or other genetic information to create a new 
replication competent virus that continues to be shed by the study individual, 
it is theoretically possible that either vector or a new replication competent 
virus could be released to the environment. Together, the available data ar- 
gues that this theoretical possibility does not pose a risk to the environment 
should it occur. 
9.5 Risk-Benefit Considerations for the Patient. If successful, administration 
of the AdcvCFTR.10 to the airways will result in expression of normal CFTR 
protein in the respiratory epithelium, with normalization of cAMP- regulated 
Cl' secretion, that is, it will correct the major biochemical abnormality as- 
sociated with CF. If these changes are extensive enough they may result in 
normalization of the airway surfaces of the treated areas and in clinical im- 
provement in the study subject. Such a clinical change is possible but by no 
means certain, and will likely depend on the percentage of corrected cells. 
Furthermore while such biologic or clinical change may persist for a signifi- 
cant period, the fact that the adenovirus vector does not transfer genes to 
the genome of the target cells, along with the normal turnover of the respira- 
tory epithelium, suggest that therapy will have to be periodic. This protocol 
will also help define whether repeat administration of AdcvCFTR.10 is feasible 
and efficacious. 
Weighed against these potential benefits are certain risks inherent in the 
protocol which may be divided into two main types: (1) general risks, unre- 
lated to AdcvCFTR.lO administration per se but which occur secondary to the 
many procedures involved in evaluations throughout the protocol; and (2) risks 
associated with Ad^vCFTR-lO itself. The "general" risks are detailed in the 
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