Recombinant DNA Advisory Committee - 06/1-2/92 
investigators have shown that they can transduce primary human neuroblastoma cells and 
establish cell lines from approximately 75% of the patients. Following G418 selection of 
these cells, IL-2 expression was observed. The investigators have demonstrated that 
tumor specific cytotoxicity by peripheral blood lymphocytes (PBL) is enhanced in the 
presence of these IL-2 secreting neuroblastoma cells. 
Dr. Parkman summarized the protocol. Cell lines will be established from patients who 
have relapsed following initial chemotherapy or have progressive neuroblastoma 
following autologous bone marrow transplantation. Following transduction of these cell 
lines with the IL-2 secreting vector, clones will be selected that produce greater that 150 
picograms of IL-2 per milliliter in 24 hours. The patients will receive two injections of 
transduced cells at one week intervals and will not receive concomitant chemotherapy. 
Dr. Parkman said that besides examining patients for the usual toxicity endpoints, the 
investigators will monitor systemic effects caused by the production of IL-2 and possible 
local tumor growth. It is important to remember that these patients have bulk disease 
and that any tumor being reinfused is minuscule compared to the total tumor burden. If 
a therapeutic response is observed with 10 5 cells per kilogram, then the protocol will 
proceed using 10 6 cells per kilogram. If three patients receive 10 s cells without any side 
effects, future patients will receive the higher number of cells. If there is evidence of 
local tumor growth as demonstrated by biopsy, patients will receive irradiation or 
chemotherapy. 
Dr. Parkman concluded his review by requesting that the investigators provide any pre- 
existing data that is available from their previously approved protocol. This protocol is 
scientifically sound, and the experimental design is appropriate for a Phase I study as 
proposed. 
Review- Dr. DeLeon 
Dr. DeLeon noted that the investigators have extensive experience with this ex vivo 
retroviral model, and that a significant amount of preliminary work has been performed. 
In particular, the investigators have demonstrated IL-2 expression in the transduced cell 
population. The challenge for the investigators is to inject these transduced cells 
subcutaneously into patients and demonstrate safety and efficacy. 
Dr. DeLeon stated her concerns regarding the stable expression of IL-2 in vivo. 
However, this minor weakness of the proposal does not detract from the strengths of the 
protocol particularly since these patients are refractory to conventional therapy and have 
a poor prognosis. 
Dr. DeLeon stated that this procedure may not offer a cure for these patients, but the 
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