Scientific Abstract 
SCIENTIFIC ABSTRACT 
A Phase I/Ib trial using neuroblastoma ceUs genetically engineered to express gamma interferon 
(IFN-y), using a retroviral vector is proposed, in an effort to achieve a therapeutic antitumor 
immune response. Neuroblastoma is the most common extracranial solid tumor of childhood. 
Sixty percent of neuroblastoma patients are at risk for developing fatal progressive disease. 
Despite the success of induction chemotherapy/myeloablative therapy and autologous transplant in 
attaining complete clinical remissions in the high risk group, approximately 60% develop 
progressive disease and die. Treatment with retroviral vector mediated transfer/expression of y- 
EFN into neuroblastoma cells, is proposed as a means of evoking an active immune response. 
Autologous neuroblastoma cells will be engineered to express y-IFN where available. If 
autologous neuroblastoma cells are not available, single HLA haplotype matched allogeneic cells 
will be used as an immunogen. Patients at high risk of relapse with minimal or no detectable 
disease following myeloablative therapy and autologous bone marrow transplant, or patients with 
progressive/persistent disease despite conventional therapy will be serially immunized with 
autologous/allogeneic neuroblastoma cells engineered to express y-IFN. Tumor cell lines will be 
established from tumor tissue or bone marrow metastasis, transduced with y-IFN vector, and 
transduced cells selected for G418. Levels of y-IFN production, MHC-I and MHC-II expression 
wiU be characterized. Following selection, and characterization, transduced cells will be lethally 
irradiated prior to use as an immunogen. The study will characterize safety/toxicity, clinical, and 
biological (immune) response. 
Recombinant DNA Research, Volume 19 
[87] 
