Recombinant DNA Advisory Committee - 06/7-8/93 
passed by a vote of 19 in favor, 0 opposed, and 2 abstentions. 
XX. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE THERAPY PROTOCOL ENTITLED: USE OF A RETROVIRAL VECTOR TO 
STUDY THE TRAFFICKING PATTERNS OF PURIFIED OVARIAN TIL 
POPULATIONS USED IN INTRAPERIT ONEA L ADOPTIVE IMMUNOTHERAPY OF 
OVARIAN CANCER PATIENTS - A PILOT STUDY /DR. FREEDMAN 
Review— Dr. DeLeon 
Dr. Walters called on Dr. DeLeon to present her primary review of the protocol 
submitted by Dr. Ralph S. Freedman of the University of Texas MD Anderson Cancer 
Center, Houston, Texas. Dr. DeLeon stated that this pilot study proposes the use of 
gene marking to monitor the trafficking patterns of purified tumor infiltrating 
lymphocytes (TTL) that are employed in the treatment of patients with epithelial ovarian 
carcinoma. The first objective of this study is to determine whether purified 
CD3( + )/CD8( + ) ovarian TIL, which have been expanded in IL-2, can be transduced 
with the GINa retrovirus vector carrying the neomycin resistant (neo R ) gene. Secondly, 
the PI will determine the distribution and survival of the transduced cells following 
intraperitoneal injection. The PI plans to study a total of 20 patients. TIL will be 
obtained from tumor specimens at the time of surgery, expanded in tissue culture, and 
returned to patients. At 1, 2, and 3 months post-TTL administration, a group of 6 
patients will undergo surgical biopsy at the site of tumor and surrounding normal tissue 
to monitor for neo* by PCR. The proportion of CD8( + ) and CD4( + ) cells will be 
monitored by fluorescence activated cell sorter analysis. She stated that this proposal is 
a straightforward gene marking protocol and presents no major concerns since it is 
similar to other previously approved protocols. Dr. DeLeon posed two minor issues: (1) 
omission of the required written report of adverse reactions to ORDA in the Points to 
Consider, and (2) the requirement that patients must bear the cost of the investigational 
agents and procedures. The PI agreed that this requirement is inappropriate, and that 
this section of the Informed Consent document will be amended. 
Review-Dr. Chase 
Dr. Chase stated that the protocol is poorly written; there is no clear description of the 
structure of the experiment. Dr. Chase expressed great doubt about the validity of the 
proposed statistical considerations of the experimental results. He raised five major 
concerns: (1) The treatment plan is not uniform. (2) Standard oncologic treatment is 
indistinguishable from the experimental procedures. (3) The Informed Consent 
document is unclear and requires patients to bear some of the experimental costs. (4) 
The IBC placed a contingency on approval of the protocol, yet the PI has stated that the 
contingency has been met, and (5) The discussion of the expected outcome is different 
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Recombinant DNA Research, Volume 17 
