Recombinant DNA Advisory Committee - 2/4/91 
next meeting. 
Dr. McGarrity then called a 15 minute recess for coffee and asked the committee to 
reassemble at 10:30 a.m. 
Dr. McGarrity called the committee back to order after the morning recess and called on 
Dr. Gellert to present the next agenda item. 
VI. PROPOSED ADDITION TO APPENDIX D OF THE "NIH GUIDELINES" 
REGARDING A HUMAN GENE TRANSFER PROTOCOL ENTITLED "THE 
ADMINISTRATION OF INTERLEUKIN-2, INTERLEUKIN-4, AND TUMOR 
INFILTRATING LYMPHOCYTES TO PATIENTS WITH MELANOMA": 
Dr. Gellert said that this proposal was very similar to the first approved protocol using a 
neomycin resistance gene to mark TILs in melanoma patients. Tlie main difference was 
that the cells would be cultured in IL-4, and that IL-4 would also be administered to 
patients. He said that Dr. Lotze had given assurance that IL-4 had already been used at 
NIH to expand cells in culture. However, data on such experiments had never been 
reviewed by the RAC, and Dr. Gellert suggested that it may be useful to have 
information on any significant differences that had been noted when using the IL-2/IL-4 
cell expansion. 
Dr. Gellert questioned the rationale contained in the protocol for dose escalation which 
called for escalation to continue unless 100% of patients reached Grade IV toxicity and 
asked for further discussion on this issue. Further, the protocol was unclear as to the 
doses of cells to be administered in this protocol. One of the new features of the 
protocol was supposed to have been that the fraction of gene-marked cells given would 
be greater than in previous protocols, using 50% of marked cells. However, the protocol 
contained a statement to the effect that a previous protocol had already been conducted 
at a 50% level. Furthermore, the protocol implied that in one experiment 100% gene- 
marked cells would be used but at a very small dose. He asked for clarification of this 
statement. 
He was not particularly concerned about using high proportions of transduced cells 
containing the neomycin resistance gene, but rather he was concerned about the 
manipulations necessary to transduce the cells and select for G418 resistance. In such 
cases, it would be difficult to ensure that the cells surviving such manipulations would 
have the same properties as the initial cells and whether their tumor homing and tumor 
killing capabilities would be the same. 
As far as the possibility of insertional mutagenesis. Dr. Gellert said that the protocol 
called for extensive testing of the cells in vitro before reinsertion. He did not know of 
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