Recombinant DNA Advisory Committee - 3/3-4/94 
Center, Houston, Texas. This protocol is a resubmission of the proposal that was 
deferred by the RAC at its June 7-8, 1993, meeting. The RAC deferred the original 
proposal based on the following: (1) inadequate data demonstrating efficient TIL 
transduction; (2) insufficient data demonstrating selectivity, i.e., specific trafficking of TIL 
to tumor sites; (3) incomplete statistical analysis; (4) the Informed Consent document 
must be revised in simplified language; and (5) concerns about patient responsibility for 
research-related costs must be addressed. The goal of this protocol is to develop TILs 
that can be adoptively transferred for the treatment of ovarian carcinoma. 
Following intraperitoneal administration of neo’^ marked TIL, ovarian cancer patients 
will be monitored for specific migration of TIL to the site of the tumor. The peritoneal 
fluid and peripheral blood of these patients will be monitored for neo*^ and the number 
of CD8( + ) cells will be quantitated at 24 hours, 7 days, and 18 days. The investigators 
are capable of detecting 1 in 100,000 cells by polymerase chain reaction (PCR) analysis. 
The preclinical data demonstrated that ovarian TIL, which were expanded in low dose 
interleukin-2 (IL-2), were CD3( + ) and CD8( + ) and exhibited preferential killing of 
autologous ovarian tumor cells. A preliminary study involving TIL and 11^2 
administration to patients with advanced refractory ovarian carcinoma demonstrated an 
increase in radioactive uptake in patients' liver metastases. In this resubmission, the 
investigators have provided marginal data demonstrating their ability to detect 1 in 
100,000 neo*^ marked TIL. In Dr. Brinckerhoffs written comments, she states that the 
protocol is poorly written and the rationale for the study is poorly stated. Why has the 
proposed number of patients been reduced from 20 to 10? How will these patients be 
selected? The investigators' written response to Dr. Brinckerhoffs comments state that 
they are able to obtain 10 to 12% transduction efficiency; however, supporting data was 
not submitted. Most of the issues raised by Dr. Brinckerhoff remain outstanding. 
Review-Dr. Dronamr^u 
Dr. Dronamraju raised several issues that must be addressed by the investigators: (1) 
the statement in the Informed Consent document that explains that the patient cannot be 
reimbursed for any costs associated with research related injuries, (2) the transduction 
efficiency must be supported by adequate data, (3) data must be submitted 
demonstrating that TIL trafficking can be distinguished between tumor and adjacent 
normal tissues by PCR, and (4) the investigator's statement regarding lack of necessity in 
determining whether transgene expression should be clarified. 
Review-Dr. Secundy 
Dr. Secundy commented that the Informed Consent document was not written in 
language understandable to laypersons. There is no clear description of the experiments 
that will be performed, and there are several inconsistences between the Informed 
Consent document and the protocol, e.g., possible side effects. 
Dr. Secundy summarized the written comments submitted by Ms. Meyers. The Informed 
Consent document language should be simplified. Patients should not be required to 
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