Recombinant DNA Advisory Committee - 3/3-4/94 
change in Dr. Rosenberg's study (Protocol #9007-003), Dr. Walters said that the minor 
modification was approved by the ORDA on February 17, 1994. 
V. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED; A PHASE I STUDY OF 
IMMUNIZATION WITH GAMMA INTERFERON TRANSDUCED NEUROBLASTOMA 
CELLS /DRS. ROSENBLATT AND SEEGER 
Review— Dr. Smith 
Dr. Walters called on Dr. Smith to present his primary review of the protocol submitted 
by Dr. Joseph Rosenblatt of the University of (^lifomia, Los Angeles, California, and 
Dr. Robert Seeger of Children's Hospital, Los Angeles, California. Dr. Smith explained 
that neuroblastoma is the most common extracranial solid tumor in children. 
Autologous or allogeneic neuroblastoma cell lines will be transduced with the retroviral 
vector, PHU-y-IFN, that expresses gamma (y) interferon. The transduced cells will be 
lethally irradiated and injected subcutaneously into patients with the objective of 
inducing an enhanced antitumor response. Both the retroviral vector, pHU-y-IFN, and 
the packaging cell line, VCHU, were previously approved by the RAC for Dr. Seigler's 
melanoma study (Protocol #9306-043). A total of 18 patients under 21 years of age will 
be divided into two groups: (1) those demonstrating no evidence of disease but who are 
at significant risk for recurrence or who demonstrate minimal residual disease following 
the standard chemotherapy and autologous bone marrow transplant regimen; and (2) 
those who demonstrate persistent or progressive disease. Three dose levels for injections 
are defined, and 3 patients from each clinical subgroup will be entered at each dose 
level. A detailed "stop rule" is defined for the trial. The study will characterize safety, 
toxicity, and clinical antitumor responses. Autologous neuroblastoma cells will be 
transduced if possible; however, if autologous cells are unavailable, allogeneic cells will 
be used that have a single human leukocyte antigen (HLA) haplotype match. 
Dr. Smith stated that the investigators have provided satisfactory responses to the 
questions raised in the primary written review of this protocol. The investigators have 
provided the following subsequent information: (1) data demonstrating that the 
transduced neuroblastoma cells have been lethally irradiated, (2) data demonstrating that 
lethally irradiated transduced cells continue to express adequate levels of IFN-y, (3) data 
demonstrating a 50% success rate in establishing primary neuroblastoma cell lines, and 
(4) data demonstrating efficient transduction of these primary cell lines. Dr. Smith 
recommended approval of the protocol. Dr. Smith asked the Principal Investigator to 
comment on the other ongoing melanoma study employing the same retroviral vector 
(Dr. Seigler's Protocol #9306-043). 
Review-Dr. Chase (presented by Dr. Smith) 
Dr. Chase's written comments stated that this protocol is similar to other protocols 
previously approved by the RAC, and the vector and packaging cell line are identical to 
those approved for Dr. Seigler's study (Protocol #9306-043). Therefore, there are no 
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Recombinant DNA Research, Volume 19 
