Recombinant DNA Advisory Committee - 6/9-10/94 
abstention, RAC approval is contingent on the following: (1) the vector construct 
encoding the HSV-TK gene will not be used, (2) submission of data (a minimum of 4 
reproducible experiments) demonstrating efficient transduction of human synovial cells 
with the vector that will be used in the human protocol, and (3) submission of safety 
data demonstrating that transduced synovial cells expressing IRAP do not traffic to other 
sites following intra-joint injection. 
VI. ADDITION TO APPENDIX D OF THE NIH GUIDELINES REGARDING A HUMAN 
GENE TRANSFER PROTOCOL ENTITLED: USE OF A RETROVIRAL VECTOR TO 
STUDY THE TRAFFICKING PATTERNS OF PURIFIED OVARIAN TIL 
POPULATIONS USED IN INTRAPERITONEAL ADOPTIVE IMMUNOTHERAPY OF 
OVARIAN CANCER PATIENTS: A PILOT STUDY /DJL FREEDMAN 
Review-Dr. Dronamraju 
Dr. Walters called on Dr. Dronamraju to present his primary review of the protocol 
submitted by Dr. Ralph Freedman of MD Anderson Cancer Center, Houston, Texas. 
This protocol is a resubmission of the proposal that was deferred by the RAC at its June 
7-8, 1993, and March 3-4, 1994, meetings. The RAC deferred the protocol at its March 
1994 meeting until the investigator returned to the full RAC with the following: (1) a 
modified protocol that includes a revised treatment schema, and (2) a revised Informed 
Consent document that describes the clinical procedures to be performed in language 
that is understandable to laypersons. 
Dr. Dronamraju said that most of the previous questions raised by the reviewers have 
been answered by the investigator. The investigator has agreed to choose 1 month after 
infusion of the marked tumor infiltrating lymphocytes (TIL) as the time point for marker 
detection rather than 2 to 3 months as previously proposed. In response to Dr. 
Brinckerhoffs previous concerns, the investigator has clearly defined a successful 
outcome of gene marking. The specific uptake of marked TIL at the tumor sites will be 
supported when the mean numbers of marked cells in tumor tissue is significantly larger 
than the mean number of marked cells in the normal tissues. Dr. Dronamraju asked the 
investigator to clarify the meaning of their response to Dr. Brinckerhotfs review that 
"5% of the infected cells being marked, 9 evaluable patients will provide me anin gful 
answer." In response to Dr. Brinckerhoffs written comments, the investigator has 
submitted polymerase chain reaction (PCR) assay data demonstrating his ability to detect 
1 neomycin resistance (neo^) marked cell in 1 x 10^ cells. 
Dr. Dronamraju noted Ms. Meyers' written suggestion that the Informed Consent 
document should be revised such that patients will not be expected to pay for any 
research-related costs. The investigator indicated in his written response that the 
difficulties encountered previously in transducing CD8( + ) cells have been overcome. 
Overall, Dr. Dronamraju said that all reviewers are in agreement that most questions 
have been answered satisfactorily. 
Review-Dr. Brinckerhoff (presented by Dr. Dronamr^u) 
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Recombinant DNA Research, Volume 19 
