Characterizing the anti-tumor function of adoptively transferred NK cells in vivo
Hollie J Pegram, Nicole M Haynes, Mark J Smyth, Michael H Kershaw, Phillip K Darcy
CANCER IMMUNOLOGY IMMUNOTHERAPY | SPRINGER | Published : 2010
Natural killer (NK) cells represent a promising cell type to utilize for effective adoptive immunotherapy. However, little is known about the important cytolytic molecules and signaling pathways used by NK cells in the adoptive transfer setting. To address this issue, we developed a novel mouse model to investigate the trafficking and mechanism of action of these cells. We demonstrate that methylcholanthrene-induced RKIK sarcoma cells were susceptible to NK cell-mediated lysis in vitro and in vivo following adoptive transfer of NK cells in C57BL/6 RAG-2(-/-)gammac(-/-) mice. Cytotoxic molecules perforin, granzymes B and M as well as the death ligand TRAIL and pro-inflammatory cytokine IFN-ga..View full abstract
We would like to acknowledge the assistance of the Peter MacCallum Cancer Centre Experimental Animal Facility technicians for animal care, in particular Michelle Stirling and Leanne McNiff for maintenance of the gene-targeted mice used in this study. We would also like to acknowledge Nicole McLaughlin for generating some of the antibodies used in these experiments. This work was funded by project grants from the National Health and Medical Research Council (NHMRC), Cancer Council of Victoria and the Susan Komen Breast Cancer Foundation. M. H. Kershaw and P. K. Darcy were supported by a NHMRC Senior Research Fellowship and Career Development Award, respectively. M.J. Smyth was supported by a NHMRC Senior Principal Research Fellowship. N.M. Haynes was supported by a NHMRC CJ Martin Fellowship.