ALL STEM CELLS

Adoptive Transfer of Gene-Modified Primary NK Cells Can Specifically Inhibit Tumor Progression In Vivo 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- signaling domains (scFv-CD28-). In this study we demonstrated that mouse NK cells gene-modified with this chimera could specifically mediate enhanced killing of an erbB2 MHC class I lymphoma in a perforin-dependent manner. Expression of the chimera did not interfere with NK cell-mediated cytotoxicity mediated by endogenous NK receptors. Furthermore, adoptive transfer of genemodified NK cells significantly enhanced the survival of RAG mice bearing established i.p. RMA-erbB2 lymphoma.

In summary,
these data suggest that use of genetically modified NK cells could broaden the scope of cancer immunotherapy for patients. The Journal of Immunology, 2008, 181: 3449–3455.
Natural killer cells comprise 5–10% of PBLs and play an important role in the body’s first line of defense against pathogen invasion and malignant transformation (1, 2).
Unlike the exquisite Ag specificity observed for T and B lymphocytes, NK cells instead express a number of different activation and inhibition receptors which provide a balance of signals that
dictate their overall response (3).

Source : http://www.jimmunol.org/cgi/content/full/181/5/3449