Abstract
Efforts at harnessing the antitumour activity of natural killer (NK) cells have been investigated for the immunotherapy of human cancer for over two decades. Initial trials, focusing on the use of ex vivo-generated lymphokine activated killer (LAK) cells or activated NK cells, or in vivo cytokine therapy to expand and activate NK cells against autologous tumours, have yielded only modest success. Recent understanding of the means by which NK cells kill target cells through a complex set of activating and inhibitory receptors recognising corresponding ligands on tumour cells has paved the way for the design of improved strategies for NK cell-based immunotherapy. The net balance of activating and inhibitory signals through NK cell receptors determines whether an NK cell becomes activated or not. Successful therapeutic strategies should now focus on manipulating the balance in favour of activating receptor signalling. In the case of autologous cancers, such strategies may include the use of monoclonal antibodies with cytokines to better direct NK cells to their tumour targets through the process of antibody-dependent cellular cytotoxicity (ADCC) or the in vivo blocking of inhibitory interactions between NK receptors (NKRs) and ligands on tumour cells. Alternatively, allogeneic NK cells can be used whenever there is mismatching of inhibitory NK cell receptors and ligands. Finally, methods to modulate expression of NK cell receptors and their ligands on tumour cells by cytokines and other agents should be explored. In this review, the impact of NKR biology on the development of novel strategies for the use of NK cells in the treatment of human cancer is discussed.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 237-250 |
| Number of pages | 14 |
| Journal | Expert Opinion on Biological Therapy |
| Volume | 3 |
| Issue number | 2 |
| DOIs | |
| State | Published - Apr 2003 |
| Externally published | Yes |
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Keywords
- Cancer
- Immumotherapy
- Interleukin-2
- NK cells
- Transplantation
ASJC Scopus subject areas
- Pharmacology
- Biochemistry, Genetics and Molecular Biology(all)
- Genetics
- Immunology
Cite this
New directions in natural killer cell-based immunotherapy of human cancer. / Farag, Sherif; Fehniger, Todd A.; Becknell, Brian; Blaser, Bradley W.; Caligiuri, Michael A.
In: Expert Opinion on Biological Therapy, Vol. 3, No. 2, 04.2003, p. 237-250.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - New directions in natural killer cell-based immunotherapy of human cancer
AU - Farag, Sherif
AU - Fehniger, Todd A.
AU - Becknell, Brian
AU - Blaser, Bradley W.
AU - Caligiuri, Michael A.
PY - 2003/4
Y1 - 2003/4
N2 - Efforts at harnessing the antitumour activity of natural killer (NK) cells have been investigated for the immunotherapy of human cancer for over two decades. Initial trials, focusing on the use of ex vivo-generated lymphokine activated killer (LAK) cells or activated NK cells, or in vivo cytokine therapy to expand and activate NK cells against autologous tumours, have yielded only modest success. Recent understanding of the means by which NK cells kill target cells through a complex set of activating and inhibitory receptors recognising corresponding ligands on tumour cells has paved the way for the design of improved strategies for NK cell-based immunotherapy. The net balance of activating and inhibitory signals through NK cell receptors determines whether an NK cell becomes activated or not. Successful therapeutic strategies should now focus on manipulating the balance in favour of activating receptor signalling. In the case of autologous cancers, such strategies may include the use of monoclonal antibodies with cytokines to better direct NK cells to their tumour targets through the process of antibody-dependent cellular cytotoxicity (ADCC) or the in vivo blocking of inhibitory interactions between NK receptors (NKRs) and ligands on tumour cells. Alternatively, allogeneic NK cells can be used whenever there is mismatching of inhibitory NK cell receptors and ligands. Finally, methods to modulate expression of NK cell receptors and their ligands on tumour cells by cytokines and other agents should be explored. In this review, the impact of NKR biology on the development of novel strategies for the use of NK cells in the treatment of human cancer is discussed.
AB - Efforts at harnessing the antitumour activity of natural killer (NK) cells have been investigated for the immunotherapy of human cancer for over two decades. Initial trials, focusing on the use of ex vivo-generated lymphokine activated killer (LAK) cells or activated NK cells, or in vivo cytokine therapy to expand and activate NK cells against autologous tumours, have yielded only modest success. Recent understanding of the means by which NK cells kill target cells through a complex set of activating and inhibitory receptors recognising corresponding ligands on tumour cells has paved the way for the design of improved strategies for NK cell-based immunotherapy. The net balance of activating and inhibitory signals through NK cell receptors determines whether an NK cell becomes activated or not. Successful therapeutic strategies should now focus on manipulating the balance in favour of activating receptor signalling. In the case of autologous cancers, such strategies may include the use of monoclonal antibodies with cytokines to better direct NK cells to their tumour targets through the process of antibody-dependent cellular cytotoxicity (ADCC) or the in vivo blocking of inhibitory interactions between NK receptors (NKRs) and ligands on tumour cells. Alternatively, allogeneic NK cells can be used whenever there is mismatching of inhibitory NK cell receptors and ligands. Finally, methods to modulate expression of NK cell receptors and their ligands on tumour cells by cytokines and other agents should be explored. In this review, the impact of NKR biology on the development of novel strategies for the use of NK cells in the treatment of human cancer is discussed.
KW - Cancer
KW - Immumotherapy
KW - Interleukin-2
KW - NK cells
KW - Transplantation
UR - http://www.scopus.com/inward/record.url?scp=0037391786&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037391786&partnerID=8YFLogxK
U2 - 10.1517/14712598.3.2.237
DO - 10.1517/14712598.3.2.237
M3 - Article
C2 - 12662139
AN - SCOPUS:0037391786
VL - 3
SP - 237
EP - 250
JO - Expert Opinion on Biological Therapy
JF - Expert Opinion on Biological Therapy
SN - 1471-2598
IS - 2
ER -