Recombinant DNA Advisory Committee - 10/7-8/91 
Dr. Post asked if there exists animal data to show that it is better to use TNF than IL-2. 
Dr. Rosenberg said he is in the process of trying to compare them in the animal models, 
but there is no question that in both systems one can raise highly cytolytic cells with 
specificity for tumor antigens. 
Dr. Mclvor asked if the preclinical data in animals has been done with clones of tumor 
cells that have been transduced and then selected to secrete an optimized level of 
cytokines. The proposal calls for establishing a heterogeneous transduced cell population 
where there will be a wide variety of levels of expression from one cell to the next within 
the population. Dr. Rosenberg replied that they have criteria for selection of the bulk 
population. If possible, a heterogeneous population will be used to get as many of the 
antigens that would be present on the original tumor as possible. The human cells have 
not been selected, but the bulk populations do make a large amount of TNF. There has 
to be a minimum, and there is no need to administer cells that are not making enough 
TNF. Hopefully, correlations can be drawn as to how much is needed to see an anti- 
tumor effect. If there are some non-TNF producing cells in the mixture, they should be 
eliminated by the immune system. 
Dr. Leventhal moved that the treatment of five patients on the protocol with TNF- 
modified tumor cells be approved with further approval contingent on Dr. Rosenberg 
reporting back to the RAC on the side effects in these first five patients. Dr. Mclvor 
seconded the motion. 
Dr. B. Murray called for further discussion. There being none, the motion was put to a 
vote. The motion passed by a vote of 17 in favor, 0 opposed, and 1 abstention. 
Dr. Leventhal asked. Dr. Rosenberg to summarize the difference between the IL-2 study 
and the TNF study. 
Dr. Rosenberg said the protocols are virtually identical with the exception of the few 
paragraphs that substitute the word TNF for IL-2. Since the tumors do not grow in 
either case, it is not expected to be any significant toxicity due to the production of the 
cytokine by the tumor. There are no potential problems with IL-2 that would be 
different than those of TNF, but it is impossible to predict relative efficacy. 
Dr. Kelley asked if the investigators were pursuing both experiments simultaneously to 
enhance the likelihood of a positive outcome. Dr. Rosenberg replied that was his 
intention. Dr. Leventhal asked if there are positive outcomes in both treatments. What 
are the future plans for doing this double-armed experiment? Dr. Rosenberg said he 
would vigorously pursue them both or exploit animal models to help develop 
improvements. Dr. Leventhal said that if there are positive results from the first five 
patients, a specific outline should be submitted of their future plans. This should include 
Recombinant DNA Research, Volume 15 
[25] 
