| First Author | Bevaart L | Year | 2006 |
| Journal | Br J Haematol | Volume | 132 |
| Issue | 3 | Pages | 317-25 |
| PubMed ID | 16409296 | Mgi Jnum | J:105075 |
| Mgi Id | MGI:3613400 | Doi | 10.1111/j.1365-2141.2005.05884.x |
| Citation | Bevaart L, et al. (2006) Direct targeting of genetically modified tumour cells to Fc gammaRI triggers potent tumour cytotoxicity. Br J Haematol 132(3):317-25 |
| abstractText | Expression of the type I receptor for Fc domain of immunoglobulin (Ig)G (Fc gammaRI or CD64) is restricted to myeloid effector cells, such as monocytes, macrophages and a subset of dendritic cells. Previous work has indicated a role for Fc gammaRI in antibody-dependent phagocytosis and lysis of tumour cells. We hypothesised that tagging of tumour cells with an anti-Fc gammaRI single chain Fv (sFv) may facilitate targeting to this receptor on effector cells, thereby initiating tumour cytotoxicity. A vector encoding the sFv for an Fc gammaRI-specific antibody (H22), linked to the transmembrane domain of platelet-derived growth factor was constructed. Transfected tumour cells expressed high surface levels of functional H22-sFv, which greatly enhanced susceptibility for phagocytosis and lysis by monocytes and macrophages. The expression of H22-sFv evoked the ability of tumour cells to directly activate monocytes, as evidenced by phosphorylation of mitogen-activated protein kinase and secretion of the inflammatory cytokines interleukin (IL)-1beta, tumour necrosis factor-alpha and IL-6. Moreover, growth of tumour cells in mice expressing H22-sFv was profoundly delayed (or absent) in transgenic mice expressing human Fc gammaRI. These results demonstrated that tumour cells can be readily modified to activate cell effector mechanisms, a strategy that may be useful for in vivo targeting in patients. |
