Human Gene Therapy Subcommittee - 11/30/90 
these discussions should be correlated with the RACs attempt to look at its future 
role in biotechnology, and that these issues may be better discussed at the parent 
committee. 
Dr. Walters thanked Mr. Capron for bringing these long-term issues to the attention 
of the HGTS, and a time should be allotted at the next HGTS meeting to discuss 
this issue. 
VII. PROPOSED ADDITION TO APPENDIX D OF THE NIH GUIDELINES 
REGARDING HUMAN GENE THERAPY PROTOCOL ENTITLED THE 
ADMINISTRATION OF INTERLEUKIN-2, INTERLEUKIN-4 AND TUMOR 
INFILTRATING LYMPHOCYTES TO PATIENTS WITH MELANOMA 
Dr. Walters called on Dr. Parkman to begin the discussion on the next protocol. Dr. 
Parkman said that IL-4 was a substance made by T cells which originally was thought 
to be related to the ability of B cells to make antibodies. However, research has 
shown that in murine systems it also plays a part in the production of cytotoxic T 
cells. This finding led to the basic premise of the study under consideration that 
when \LA is added to TILs in addition to IL-2, the therapeutic response will be 
improved. 
Dr. Parkman said the protocol has four parts, three of which concern giving IL-2 and 
IL-4 to a variety of cancer patients, which is outside the purview of the HGTS. The 
fourth part is similar to the original Rosenberg TIL cell marking protocol and would 
consist of marking cells with the neomycin resistance gene and reinfusing with a 
combination of IL-2 and IL-4, The only difference between this protocol and the 
original Rosenberg protocol is the addition of the IL-4. IL-4 is being added to see if 
the combination of IL-2 and IL-4 will result in a larger percentage of people with 
partial or complete responses. 
Dr. Parkman noted that a variety of questions were forwarded to the investigators to 
which they had responded. The only question of a scientific nature that still remains 
unanswered is the discrimination between marked TIL cells in the tumor and cells 
passing through the tumor randomly via the peripheral blood. There are two basic 
scientific questions that need to be answered: (1) Does the addition of IL-4 lead to 
a better clinical response? and (2) Is there true homing in the sense that the 
frequency of neomycin-containing cells in the tumor is greater than what would be 
expected on a random basis from circulation? Dr. Parkman asked Dr. Lotze to 
address these specific topics in his comments. 
Recombinant DNA Research, Volume 14 
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