Human Gene Therapy Subcommittee - 11/21-22/91 
Dr. Walters called on Dr. Miller to present his primary review of the protocol submitted 
by Dr. Economou of the University of California, Los Angeles. Dr. Miller said that this 
protocol involves genetic marking of tumor-infiltrating lymphocytes (TILs) and peripheral 
blood lymphocytes (PBLs) with retroviral markers to follow their persistence and 
distribution in patients with melanoma and renal cell cancer. This protocol is similar to 
one submitted by Rosenberg, et aL, using TILs marked with the LNL6 vector. The 
Rosenberg protocol was reviewed and approved by the HGTS and the RAC. Dr. 
Economou's protocol proposes to mark various cell populations using LNL6 and a new 
vector, GINa. Dr. Miller stated that the GINa retroviral vector is probably safer than 
LNL6. 
Dr. Miller thought that the protocol was adequately documented, including the Points to 
Consider in the Design and Submission of Protocols for the Transfer of Recombinant DNA 
into the Genome of Human Subjects (Points to Consider) section. The objective is to 
establish which cell populations would provide the most effective form of treatment by 
marking them independently with separate vectors and following them in the patient. 
There will be six different sub-populations of cells isolated: total TILs, CD8( + ) TILs, 
CD4( + ) TILs, total PBLs, CD4( + ) PBLs, and CD8( + ) PBLs. 
Dr. Miller said that the investigators will use a device called a Cellector® to isolate the 
various subpopulations of lymphocytes. This gene marking experiment will use a total of 
six cell populations; each population will be marked with either the LNL6 or GINa 
retroviral vector to assess homing of these cells to tumor in patients. He asked if the 
Cellector® had been approved for use by the Food and Drug Administration (FDA). 
The investigators indicated yes, and that they would present an FDA approval or have 
information pertaining to FDA's approval of this device. 
Dr. Miller said that it was unfortunate that for the analysis the investigators had chosen 
polymerase chain reaction (PCR) primers that were the same fragment size. Since the 
primers are the same size, two separate amplifications will be necessary for each 
population of cells. The investigators have stated that they may address this problem in 
the future, but that they intend to proceed with the PCR analysis using the primers 
described in this protocol. Dr. Miller asked the investigators where the PCR analysis 
will be performed. Dr. Miller said that although the investigator states that these assays 
will be performed in his own laboratory, the pictures submitted to the HGTS for review 
are uninterpretable. The investigators need to provide more primary PCR data during 
their presentation. 
The investigators also need to provide safety data on the GINa vector. There is no 
reason to believe that this new vector should have any risks associated with it over 
LNL6. However, the HGTS ought to have access to these safety data. 
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