Recombinant DNA Advisory Committee - 6/9-10/94 
insist on using mice, the C57/Black strain is preferable. 
Dr. Miller raised a concern about spreading of the adenovirus vector carrying a mutated 
p53 gene with oncogenic potential to cells outside the injected areas or to other 
individuals. The safety data presented did not rule out the generation of mutant virus in 
the vector preparations. Dr. Roth disagreed with Dr. Miller's interpretation stating that 
cells transduced for 2 weeks should not have any oncogenic potential. Dr. Smith 
suggested that subjects should be monitored for virus shedding. Dr. Miller suggested and 
Dr. Roth concurred that patient's sputum will be collected and assayed for the presence 
of adenovirus on 293 cells expressing the viral Ela and Elb genes. 
Committee Motion 
The RAC approved a motion made by Dr. Parkman and seconded by Dr. Haselkom to 
accept the protocol submitted by Dr. Jack A Roth of M.D. Anderson Cancer Center, 
Houston, Texas, by a vote of 11 in favor, 1 opposed, and 1 abstention. Approval of the 
protocol is contingent on the review and approval of the following by the primary RAC 
reviewers: (1) Intra-pleural administration of the adenovirus vector will be eliminated 
from the protocol; therefore, a revised protocol and Informed Consent document are 
required; and (2) The protocol will be revised to include patient sputum titration assays 
of the adenovirus on 293 cells (for both the wildtype and vector adenoviruses) to be 
conducted until virus is no longer detectable (patients will be isolated for a period of 1 
week). 
The RAC deferred the intrapleural administration portion of the protocol until the 
investigator returns to the full RAC with a revised protocol that includes toxicity data 
demonstrating the effect of the adenovirus vector and cisplatin in an appropriate animal 
model. The RAC strongly recommended the cotton rat as the most appropriate model. 
XVI. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: INJECTION OF GLIOBLASTOMA 
PATIENTS WITH TUMOR CELLS GENETICALLY MODIFIED TO SECRETE 
INTERLEUKIN-2 (IL-2): A PHASE I STUDY/DRS. SOBOL AND ROYSTON 
Review— Dr. Miller 
Dr. Walters called on Dr. Miller to present his primary review of the protocol submitted 
by Drs. Robert Sobol and Ivor Royston of the San Diego Regional Ciicer Center, San 
Diego, California. This protocol is a resubmission of a protocol that was disapproved by 
the RAC at its December 2-3, 1993, meeting. The majority of the RAC members 
concluded that the preclinical data derived from a single patient protocol was inadequate 
to justify the proposal. 
This revised protocol involves subcutaneous injection of irradiated tumor cells secreting 
U^2 in an attempt to stimulate antitumor immuni ty in patients with glioblastoma. Both 
autologous and ^ogeneic human leukocyte antigen A2 (HLA-A2) positive tumor cells 
Recombinant DNA Research, Volume 19 
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