Recombinant DMA Advisory Committee - 3/3-4/94 
Dr. Parkman said that most of the marked TIL cells will be in the blood circulation; 
therefore, blood supply of the tissue samples will be critically important. TIL activity 
should be compared by biopsy of the omentum versus normal peritoneal tissue since the 
amount of blood supply will vary at different locations. 
Dr. Freedman presented data demonstrating the level of sensitivity of the PCR assay. 
PCR analysis detects 1 in 100,000 neo^ marked cells. Dr. Smith expressed his concern 
whether 10 patients would yield statistically significant information. Dr. Parkman 
explained that normal peritoneal tissue obtained by laparoscopy may not represent the 
best tissue for comparison since the blood supply is significantly different than that of the 
tumor. 
Dr. Chris Platsoucas of Temple University responded to questions about transduction 
efficiency. The 10 to 12% transduction efficiency data refers to primary TIL cells rather 
than to cultured cell lines. With regard to transgene expression. Dr. Freedman explained 
that this protocol is a marking study; therefore, expression is of secondary interest. 
Dr. Freedman responded to concerns about patient responsibility for some of the 
research costs. This statement in question was required by the MD Anderson Cancer 
Center's IRB and its legal counsel. Dr. Secundy asked whether such a statement is 
required for all MD Anderson Cancer Center protocols. Dr. Walters noted that this 
statement was not included in other MD Anderson Cancer Center gene marking 
protocols previously reviewed by the RAC. 
Dr. Post asked about the experimental design of this study. The schema combined 
treatment flow charts of an ongoing TIL therapy protocol with the present gene marking 
study. Drs. Post, Smith, Parkman, and Straus asked many questions in order to clarify 
how patients will be infused with the marked TIL cells and how samples will be obtained 
and analyzed. Drs. Freedman and Platsoucas attempted to clarify the uncertainty about 
the treatment schema. Dr. Motulsky recommended that the investigators submit a 
revised protocol incorporating all of the suggestions referred by the RAC. Dr. Parkman 
said that the revised protocol should include a scientific rationale that supports tissue 
sampling 90 days post-infusion. Do the neo^ sequences persist at 90 days? 
Dr. Secundy recommended that a revised Informed Consent document should be 
required that includes a clear rationale as to the purpose and schedule for all clinical 
procedures and a description of any possible risks and side effects of these procedures. 
Committee Motion 
A motion was made by Dr. Motulsky and seconded by Ms. Grossman to defer approval 
of the protocol until the investigators return 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. The motion to defer the protocol passed by a vote 
of 12 in favor, 1 opposed, and no abstentions. 
Recombinant DNA Research, Volume 19 
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