Modification of Natural Killer cells to target tumors

Abstract

The background and the aim: NK cells cytolytic and cytokine production activities suggest them as a potential source for adoptive therapy. I engineered NK cells with chimeric receptors (CARs) specific for HER-2, a tumor-associated antigen frequently overexpressed by many tumors of epithelial origin, providing them with tumor-antigen targeting specificity. Material and Methods: NK cells have been genetically modified by using the following techniques: Isolation of human PBMCs, expansion of primary human NK cells, retroviral transduction. Results: I compared first and second generation CARs including a stimulatory (CD3ζ) signaling domain alone or together with a costimulatory (CD28) signaling domain. I found that costimulatory signaling markedly improved IL-2 production by NK cells. Conclusion: Thus, the direct coupling of the antibody specificity to the function of NK cells by CAR expression is uniquely able to enhance tumor cells targeting by NK cells.