Addition to the Informed Consent (to be inserted as Indicated) 
This treatment of patients with tumor infiltrating lymphocytes can resxilt in 
a substantial decrease in tumor size in some patients. Until recently, there has 
been no method to determine how many of the lymphocytes survive, how long they 
survive, and for what period of time they continue to function after reinjection 
into the body. Learning about these aspects of the lymphocytes may help us to 
better understand how they function and allow us to Improve cancer therapy. 
This modification of the primary protocol is not expected to improve your therapy 
at this time. It is possible, however, that results of this study may lead to 
improved cancer therapies for yourself and others in the future. 
Recent scientific advances have resulted in the ability to mark or tag cells 
with a "gene" (an information molecule inserted into a chromosome of the cell) 
allowing us to later recover these cells from the body to learn more about the 
cell's life span and f^inctioning. The inserted gene allows the marked cells to 
grow in a special tissue culture solution, thereby permitting xis to distinguish 
them from other lymphocytes in the blood or tissue. If you decide to 
participate, a portion of the tumor infiltrating lymphocytes will be marked with 
a gene called N2 using a genetically altered virus. We will continue to grow the 
marked cells separately in the laboratory while they are tested to be certain 
that they are growing properly and that they are safe to return to your body. If 
no abnormalities in the cells can be identified, they will be reinfused along 
with the other standard unmarked lymphocytes at the appropriate time. 
There are some theoretical risks to this procedure. First, even though the 
virus used to insert the marker gene into your lymphocytes has been made 
defective, it is possible that events could occur within the cell resulting in 
the production of a new infectious virus or even malignant cells. To minimize 
this possibility, the gene-marked lymphocytes will be tested and if any 
abnormalities are found they will be discarded. However, since this is a new 
procedure, we do not know whether or not the marked cells might develop an 
abnormality in functioning after they have been injected. In a number of animal 
experiments , we have been unable to demonstrate either virus production or the 
development of malignant cells for greater than 2 years after treatment. In any 
case, greater than half the total number of cells given back to you will be the 
standard lymphocytes so that it is extemely unlikely that your treatment would be 
less effective. Second, the inserted gene produces a protein that inactivates 
certain antibiotics. These antibiotics are not commonly used to treat infections 
in hximans and many other antibiotics are available that will not be inactivated 
and would be effective in treating bacterial infections. We emphasize that this 
procedure, called retroviral-mediated gene transfer, has never before been \ised 
in man. Because this procedure is new it is possible that other problems may 
occur that have not been foreseen. 
Participation in this study will probably require no additional treatment or 
evaluation; Blood and tissue specimens obtained as part of the tumor 
infiltrating lymphocyte research project would be utilized to follow the life 
span and function of these marked cells. 
[18] 
Recombinant DNA Research, Volume 14 
