Human natural killer (NK) cells spontaneously lyse a wide range of tumor cell lines. This tumoricidal activity is markedly enhanced by a brief (4 hr) exposure to interleukin-2 (IL-2). IL-2 activated NK cells lyse highly resistant tumor cell lines, as well as freshly excised tumor cells. This activation requires de nova protein and RNA synthesis. Most likely, IL-2 increases the surface expression of those structures that participate in tumor cell binding and lysis. It can be postulated that IL-2 either: 1) induces the synthesis and transport of new surface structures. 2) induces a quantitative increase in the amount of pre-existing surface structures, or 3) induces a modification of pre-existing surface structures. In this proposal, those NK surface alterations that are induced by IL-2 will be identified and characterized. Cell surface biochemical techniques will be used to describe the major glycoprotein, oligosaccharide, and glycolipid constituents of unstimulated and IL-2 activated NK cells. Those surface structures that increase in response to IL-2 will be purified and tested for their ability to inhibit tumor cell binding and lysis. Antibodies have been generated against IL-2 activated NK cells and additional antibodies will be obtained. The antigens that are defined by these antibodies will be characterized. Antibodies that are specific for IL-2 activated cells will also be tested for their ability to block tumor cell interactions.
| Bagli, D J; D'Emilia, J C; Summerhayes, I C et al. (1990) c-Ha-ras-I oncogene-induced differentiation and natural killer cell resistance in a human colorectal carcinoma cell line. Cancer Res 50:2518-23 |
