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Published on: June 14, 2018
Altering the specificity of NK:target cell interactions by genetic manipulation of NK receptor expression on primary
Jimmy Tran1, Sajid Mahmood, James R Carlyle
1Room 417 Apotex Centre, Department of Immunology, University of Manitoba, 750 McDermont Avenue, Winnipeg, MB, Canada R3E 0T5.
A balance of signals generated via stimulatory and inhibitory NK receptors determines both target cell specificity and the outcome of NK-target cell interactions. The feasibility of introducing naturally occurring or genetically engineered chimeric NK receptors at the effector cell level may prove useful in NK cell-based immunotherapies. Here, we utilized a previously established lentiviral transduction system to over-express a model NKR-P1B inhibitory receptor on primary mouse NK cells. These genetically engineered NK cells became more sensitive to inhibitory signals delivered by target cells expressing the cognate NKR-P1B ligand, Ocil/Clr-b. This study demonstrated the utility of lentiviral vectors as a means to stably manipulate the target cell specificity of primary NK cells.
A balance of signals generated via stimulatory and inhibitory NK receptors determines both target cell specificity and the outcome of NK-target cell interactions. The feasibility of introducing naturally occurring or genetically engineered chimeric NK receptors at the effector cell level may prove useful in NK cell-based immunotherapies. Here, we utilized a previously established lentiviral transduction system to over-express a model NKR-P1B inhibitory receptor on primary mouse NK cells. These genetically engineered NK cells became more sensitive to inhibitory signals delivered by target cells expressing the cognate NKR-P1B ligand, Ocil/Clr-b. This study demonstrated the utility of lentiviral vectors as a means to stably manipulate the target cell specificity of primary NK cells.
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