Adoptive transfer of gene-modified primary NK cells can specifically inhibit tumor progression in vivo
Hollie J Pegram, Jacob T Jackson, Mark J Smyth, Michael H Kershaw, Phillip K Darcy
JOURNAL OF IMMUNOLOGY | AMER ASSOC IMMUNOLOGISTS | Published : 2008
NK cells hold great potential for improving the immunotherapy of cancer. Nevertheless, tumor cells can effectively escape NK cell-mediated apoptosis through interaction of MHC molecules with NK cell inhibitory receptors. Thus, to harness NK cell effector function against tumors, we used Amaxa gene transfer technology to gene-modify primary mouse NK cells with a chimeric single-chain variable fragment (scFv) receptor specific for the human erbB2 tumor-associated Ag. The chimeric receptor was composed of the extracellular scFv anti-erbB2 Ab linked to the transmembrane and cytoplasmic CD28 and TCR-zeta signaling domains (scFv-CD28-zeta). In this study we demonstrated that mouse NK cells gene-mo..View full abstract
This work was supported by a National Health and Medical Research Council Program Grant and a Cancer Council of Victoria research grant. M.H.K. and P.K.D. were supported by National Health and Medical Research Council of Australia R.D. Wright Research Fellowships. M.J.S. was supported by a National Health and Medical Research Council Senior Principal Research Fellowship.