hydroxyl at the 3’ position and are not inactivated. Therefore, introduction of 
the neo^ gene would not exclude the use of aminoglycosides or any other 
conventional antibiotic that may be needed in the clinical management of 
these patients. 
In short, the vectors to be used in this study are currently in clinical trial, and 
in extensive prior primate testing have not been associated with any adverse 
effects. 
5.0 PLAN OF CLINICAL STUDY 
5.1 Specific Inclusion and Exclusion Criteria for Gene Transduction (general 
eligibility see Section 10) 
To ensure that a sufBcient aliquot of marrow can be removed for transduction 
without potentially compromising the rate of reconstitution, the minimum 
quantity of marrow mononuclear cells to be obtained at harv'est will be raised 
by 30% above the minimum value quoted in previous neuroblastoma protocols 
(2 X 10^/kg). Should this safety margin not be attainable, the patient w'ill be 
ineligible for the transduction study. 
5.2 Preparation of Marrow 
A marrow’ mononuclear cell fraction will be obtained using a Stericell 
separator. 30% of these cells will be used for cell free vector transduction. 
The remaining marrow’ will be processed and frozen as per standard 
techniques. The aliquot will be incubated with vector containing supernatants 
and will then be frozen. The patients will be treated with chemo-radiotherapy 
as per protocol and reinfusion with the transduced and non-transduced 
marrow’ will take place as indicated in the protocols. 
6.0 EVALUATION OF EFFECTS 
6.1 Response Criteria 
Complete Response (CR): Complete resolution of all initially demonstrable 
tumor on MRI or CT evaluation without the appearance of any new areas of 
disease. 
Partial Response (PR): Greater than 50% decrease in the product of the 
p>erpendicular diameters of the tumor relative to the baseline evaluation 
without the appearance of any new’ areas of disease. 
[718] 
Recombinant DNA Research, Volume 14 
