Recombinant DNA Advisory Committee - 09/9-10/93 
typing prior to entering patients onto the study. There was a lengthy discussion about 
the scientific justification for approving this type of clinical immunotherapy trial, i.e., 
using cytokine producing cells and autologous tumor cells. Several RAC members 
expressed their reservation about the lack of any definitive result from other RAC- 
approved clinical trials that were similar to this proposal. 
Committee Motion 
A motion was made by Dr. Motulsky and seconded by Dr. Doi to approve the protocol 
contingent on review and approval of the following stipulations: (1) submission of 
transduction data on the M24 cell line, (2) an indication of the Pi's intent to perform 
HLA typing prior to enrolling the patients onto the study, and (3) submission of data 
demonstrating the biological activity of IL-2 of transduced M24 cells in the animal 
model. The motion passed by a vote of 11 in favor, 0 opposed, and 6 abstentions. 
ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING SEMLIKI 
FOREST VIRUS (SFV) VECTOR EXPRESSION SYSTEM-REDUCTION IN 
PHYSICAL CONTAINMENT FROM BL3 TO BL2/DR. TEMPLE 
Review-Dr. Miller 
Dr. Walters called on Dr. Miller to present his primary review of the proposal 
resubmitted by Dr. Gary F. Temple of Life Technologies, Inc., Gaithersburg, Maryland. 
This request was deferred at the September 14, 1992, and June 8, 1993, RAC meetings. 
The proposal was deferred during the September 1992 RAC meeting until the 
investigators return to the full RAC with data regarding the following: (1) the frequency 
of recombination that produces replication-competent virus, using cell numbers 
analogous to the laboratory setting (e.g., 1 x 10 9 cells), and (2) acquire data regarding the 
frequency of seropositivity among personnel previously exposed to SFV. The proposal 
was deferred during the June 1993 RAC meeting until the investigators could return to 
the full RAC with the following: (1) a product information sheet informing customers of 
the potential health risk of the expression system, standard methods to be used for virus 
inactivation, a helper virus assay to detect SFV, and a description of symptoms and 
procedures to be followed in the event that SFV infection occurs in a laboratory worker 
(including methods to prevent transfer to insect vectors and environmental spread); and 
(2) SFV inactivation data. 
Dr. Miller stated that the investigators are requesting a reduction in the physical 
containment level from Biosafety Level (BL) 3 to BL2 for Life Technologies' 
SFV/Helper 2 Gene Expression System. The investigators have produced a Users' 
Manual as recommended by the RAC. This manual contains the following information: 
(1) a summary of possible health risks associated with the use of the cloning system, (2) 
a description of practical and effective means to inactivate SFV, (3) a simple protocol for 
the detection of replication-competent SFV, (4) a description of symptoms associated 
with SFV infection and procedures to be followed in the event of laboratory infection. 
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