Recombinant DNA Advisory Committee - 2/10-11/92 
Dr. Mclvor asked whether the process of drawing scientific conclusions regarding TIL and 
PBL targeting could be disrupted if marked PBL were to acquire homing capabilities 
through a differentiation process or some other conditioning process. In addition, he 
asked if there was any data available concerning LAK cells homing to tumors. Dr. 
Economou explained that LAK cells are really a population of T lymphocytes, which are 
expanded over three to five days in the presence of IL-2 and have a non-MHC restricted, 
promiscuous cytotoxicity against a variety of cultured and fresh target cells. The cells 
generated in this protocol, both the TIL and the PBL, will sometimes have LAK activity. 
It is unclear whether these cells could be defined as LAK cells or are simply cells that 
grow well in IL-2. Dr. Mclvor reiterated his earlier question that if PBL are infused and 
acquire some homing capacity, would that affect interpretation of data. Dr. Economou 
responded affirmatively, however, there is no in vivo animal model that would support such 
a hypothesis. If TIL cells exhibit an anti-tumor effect either killing the tumor cells directly 
or generating cytokines that attract an inflammatory response that kills tumor cells, most 
of the models would require some enrichment or some localization of tumor. There is 
support for this theory in animal systems, and weak support in clinical systems. It is 
important to determine what is actually happening and how it correlates with clinical 
response or with a certain in vitro behavior or profile of the TILs which are administered, 
but cannot be identified. 
Committee motion 
Dr. Mclvor moved to accept the protocol, and Ms. Buc seconded the motion. Ms. Buc 
asked whether the consent form for the IL-2 or IL-2 plus IFNaA section is the same as the 
one that is already in use just for treatment purposes. Dr. Economou indicated that there 
are two separate consent forms, one for gene marking and one for treatment with IL-2 and 
IFNaA. The motion to recommend approval of the protocol carried by a vote of 15 in 
favor, 0 opposed, and no abstentions. 
Dr. B. Murray informed the RAC that Dr. Walters had agreed to lead a small working 
group comprised of Dr. Krogstad, Ms. Buc, and an FDA and NIH representative that 
would suggest standardization of protocol presentations and critiques. 
XIV. REPORT FROM THE WORKING GROUP ON DATA MANAGEMENT/AMEND 
POINTS TO CONSIDER - REPORTING REQUIREMENTS 
Report 
Dr. Leventhal reported on the Working Group on Data Management devised Forms A 
and B for investigators to report progress on their protocols to the RAC. In the past, 
investigators have delivered verbal reports but never written reports. 
Recombinant DNA Research, Volume 15 
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