Submission Co RAC (7/13/88) - Anderson/Blaese/Rosenberg 
Brief Non-Technical Description of the Proposed Experiment 
TIL (standing for tumor infiltrating lymphocyte) therapy is a new 
experimental treatment protocol for some patients who have advanced cancer. A 
portion of tumor is removed, grown in Che laboratory under conditions which allow 
the cancer cells to die, but the invading immune cells (called lymphocytes) to 
multiply. These tumor infiltrating lymphocytes are then grown in the laboratory 
to very large numbers. The TIL, which are presumed to be the patient's own 
cancer-fighting cells, are infused back into a vein of the patient. The TIL are 
thought to circulate through the body, find the areas of cancer, and then invade 
and kill the cancer cells. 
This TIL therapy has resulted in a substantial decrease in tumor size in 
about half of the patients treated thus far. Unfortunately, there has been no 
method up to now to follow and test the TIL that have been given back to a 
patient to determine why the TIL therapy works for some patients but not for 
others. The present protocol is designed to provide a means to "mark" TIL so 
that they can be isolated days or weeks later from the patient. 
The proposed method for doing this is Co mark or tag cells with a gene. The 
cell could then be recovered from the body for testing. The inserted gene would 
allow the marked cell to grow in a special culture solution in which unmarked 
cells die. 
The procedure we are proposing would be to remove some of the TIL that are 
being grown in the laboratory, insert a marker gene (in this case, a gene called 
Neo^ that provides protection from a class of toxic antibiotics) using a 
technique termed retroviral-mediated gene therapy, .and then combine these treated 
cells with the original TIL. The marked cells would act as a tracer. 
Furthermore, since the added gene becomes a permanent and stable part of the 
cell, the TIL and all its offspring would be marked in such a way that these 
cells could always, it is postulated, be identified and re- isolated even if they 
represented only a small fraction of the total cells present. 
The addition of a marker into some of the TIL would, itself, be of no 
immediate benefit to the patient in which it is used. However, the information 
obtained should be of value in helping future patients and may be beneficial in 
later therapy of the same patient. The risks to the patient should be minimal, 
and there should be no risk to other patients or to health care personnel. 
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Recombinant DNA Research, Volume 14 
