2.0 OBJECTIVES 
2.1 To determine the safety of two weekly subcutaneous (SC) injections of 
autologous neuroblastoma cells which have been modified by insertion of the 
interleukin-2 (IL-2) gene introduced by a retroviral vector. 
2.2 To determine whether MHC restricted or unrestricted anti-tumor immune 
responses are induced by SC injection of modified autologous neuroblasts and 
the cell dose required to produce these effects. 
2.3 To obtain preliminary data on the anti-tumor effects of this treatment regimen. 
3.0 BACKGROUND AND RATIONALE 
Neuroblastoma is the commonest extra-cranial solid tumor of childhood affecting 
about 500 children a year in the USA. When the tumor occurs in infants (under the 
age of 1 year) it is frequently localized and responds well to therapy. 1 Even 
disseminated disease can be eradicated in about 75% of infants, and spontaneous 
remissions are seen. 2,3 In children (over the age of 1 year), the prognosis is far worse. 4 
Although children with localized disease may still be cured by conventional therapy, 
satisfactory therapeutic approaches are lacking for those who have disseminated 
disease. 5,6 Eighty percent or more of these patients relapse within 3 years; the outlook 
after relapse is grim, with almost no long-term survivors. 4,7 Over the past decade 
attempts to improve the outcome of patients with advanced disease have concentrated 
predominantly on increasing the intensity of induction and consolidation 
chemo/radiotherapy regimens. 5 Although these efforts have increased remission rates, 
there is no evidence that they have improved long-term survival for patients with 
advanced disease. 8,9 Even the combination of autologous BMT with supralethal 
chemotherapy has failed to produce any significant survival benefit. This failure of 
conventional therapy has lead to a resurgence of interest in alternative approaches, 
the most promising of which is immune modulation. 10,11 
3.1 Evidence for a Role of the Immune System in Neuroblastoma Eradication 
The concept of utilizing the immune system for disease eradication has a long 
history in neuroblastoma research, and many aspects of tumor behavior 
support this approach. First, the tumor may spontaneously remit - particularly 
in infants. 2,3 Second, because the tumor is derived from embryonic 
neuroectoderm, it expresses antigens not widely detected on tissues in the 
"mature" child. 12 Finally, in animals and in man, neuroblastoma cells are 
susceptible to cytotoxic effector mechanisms in vitro and in vivo. 13 ' 17 
Recombinant DNA Research, Volume 15 
[747] 
