Abstract
NK92 cells genetically engineered to recognize the HER-2/neu oncoprotein have been previously reported to lyse HER-2/neu positive tumor cell lines through direct cell to cell contact. In the present study we have transduced NK92 cells with a chimeric receptor gene composed of the HER-/neu specific scFv (FRP5) antibody fragment, joined to the peptide CD8 hinge region and the signaling CD3 ζ chain. NK92 cells expressing this chimeric receptor (NK92.HER-2/neu/ζ) specifically recognized and lysed HER-2/neu overexpressing tumor cell lines both in vitro and in preclinical tumor models in vivo. More important we demonstrate that NK92.HER-2/neu/ζ cells constitutively secrete high levels of soluble scFv which mediate strong tumor cytostatic effects by directly binding on cell surface HER-2/neu. Our data uncover an additional mechanism through which NK92.HER-2/neu/ζ cells mediate antitumor effects and further support their use in cell based therapeutics for the treatment of HER-2/neu expressing cancers.
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