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Alternative triggering molecules and single chain bispecific antibodies
D M Segal1, G Sconocchia, J A Titus
1Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Journal of Hematotherapy
|October 1, 1995
Summary
Adhesion molecules like CD44 can trigger cytotoxic Natural Killer (NK) cells after IL-2 stimulation. A novel bispecific antibody redirects NK cell lysis effectively at low concentrations.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- T cell receptors and Fc receptors are known cytotoxic triggering molecules.
- Adhesion molecules are emerging as alternative triggering molecules for cell-mediated cytotoxicity.
Purpose of the Study:
- To investigate CD44 as a triggering molecule on NK cells.
- To describe a novel bispecific antibody for redirecting NK cell lysis.
Main Methods:
- Stimulation of NK cells with IL-2 to assess CD44 function.
- Production of a genetically engineered single-chain bispecific antibody in mammalian and bacterial cells.
Main Results:
- CD44 functions as a triggering molecule on NK cells post-IL-2 stimulation.
- The bispecific antibody effectively redirects NK cell-mediated lysis at nanogram per milliliter concentrations.
Conclusions:
- CD44 represents an alternative pathway for NK cell activation.
- Engineered bispecific antibodies offer potent tools for targeted cell lysis.