Biotechnology Unzipped: Promises and Realities (1997)
Joseph Henry Press (JHP)
The views expressed in this book are solely those of the author(s) and do not necessarily reflect the views of the National Academies.
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cells tumor-infiltrating lymphocytes (TILs). Unfortunately, as the tumors subsequently spread, the TILs became overwhelmed and lost the fight. To boost the body's own defense, doctors took TILs from patients, cultured them in the lab, then returned them in huge numbers to swamp the patients' lymph and blood system. About half the people with terminal melanoma (skin cancer) treated this way responded well.

The difficulty researchers had at this point was to know why some patients lost their tumors after treatment with TILs while others didn't respond at all. To find an answer they had to track TILs inside the body. However, no monitoring methods available at the time could mark the cells for longer than two weeks. After that, their fate was a mystery.

The solution eventually came as the result of a one-hour meeting between the leading TIL researcher, Steven Rosenberg (incidentally, the physician who diagnosed Ronald Reagan's cancer in 1985), and a pioneer in gene transfer experiments, William French Anderson. The two men, unaware until then of the details of one another's work, quickly devised a scheme to use altered genes for tracking TILs.

The plan was to splice a bacterial gene for resistance to a particular antibiotic into a virus, then culture the engineered virus with TILs. The virus would infect the TILs and transfer its genes onto their chromosomes. As the TILs later multiplied in culture, each would carry the telltale gene of antibiotic resistance. With this added marker, the TILs and their descendants could be tracked in tissue samples anywhere, anytime—they would be the only cells that survived when soaked in the antibiotic.


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