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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA044852-01A1
Application #
3187668
Study Section
Experimental Immunology Study Section (EI)
Project Start
1988-03-01
Project End
1991-02-28
Budget Start
1988-03-01
Budget End
1989-02-28
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02215