TIL cannot be grown in the mouse, yet they are therapeutically 
effective. Humans can have both CD4+ and CD8 + TIL. Dramatic 
anti-tumor responses have been achieved using the CD4+ TIL which 
can't be grown in the mouse, despite their having therapeutic 
effects. Therefore, Dr. Rosenberg said results in an animal 
model would not be predictive of results in man. 
Dr. Mclvor then asked how long murine TIL persisted in vivo , and 
where they persist in lymph nodes, tumor, or the bloodstream. 
Dr. Rosenberg replied that the questions had not yet been 
answered. However, given the differences between murine TIL and 
human TIL and differences between transplanted tumors in mice and 
spontaneous tumors in man, the answers in the animal model would 
still have to be corroborated in man. He noted cytokine research 
where interleukin-4 will stimulate LAK cells in mice while 
inhibiting LAK cell production in man. Dr. Mclvor said he 
thought this was the kind of discussion that needed to take place 
within the Subcommittee. 
Dr. Anderson noted that at the break he had been asked "what's 
the rush?" He said he thought it would be useful for members of 
the Subcommittee or the RAC to visit the Oncology Service of the 
NCI at the NIH Clinical Center to talk with patients dying of 
cancer and ask them the same question. 
Dr. Murray noted that in the areas of sickle cell disease 
research and vitro fertilization, where no animal models 
existed, little progress could have been made if it had been 
determined to wait for an appropriate animal model. In fact, 
progress had been achieved by taking risks. He said he felt the 
same could be done with this protocol. He likened this to early 
work with recombinant DNA where extra precautions were taken 
until the relative safety of the procedures became clear. He 
said he favored allowing "cautious proceeding" but asking at the 
same time for data in animal studies. He said, "I think we're 
placing too much emphasis on the animal experimentation, not that 
they're not important, and we have to pay more attention to the 
human situation." 
Dr. McGarrity asked if he was correct in assuming that when 
safety was being talked about that it referred to: (1) safety in 
the patient who may be living for 2 months or 3 months; or (2) 
safety in the patient who may be cured and then carry the 
retroviral vector over an extended period of time. Dr. Mulligan 
said both of these were safety concerns. Dr. Murray said some 
cancer chemotherapy regimens are very toxic and may place the 
patient at risk for cancer or other disease, but may afford them 
the chance to be cured of the primary disease. 
Dr. Kelley said this analogy didn't fit because in the protocol 
being proposed, no benefit will accrue to the patient whereas the 
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