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Review
. 2017 Aug 2;25(8):1769-1781.
doi: 10.1016/j.ymthe.2017.06.012. Epub 2017 Jun 28.

Engineering Natural Killer Cells for Cancer Immunotherapy

Katayoun Rezvani  1 , Rayne Rouce  2 , Enli Liu  3 , Elizabeth Shpall  3
Affiliations
Review

Engineering Natural Killer Cells for Cancer Immunotherapy

Katayoun Rezvani et al. Mol Ther. .

Abstract

The past several years have seen tremendous advances in the engineering of immune effector cells as therapy for cancer. While chimeric antigen receptors (CARs) have been used extensively to redirect the specificity of autologous T cells against hematological malignancies with striking clinical results, studies of CAR-modified natural killer (NK) cells have been largely preclinical. In this review, we focus on recent advances in NK cell engineering, particularly on preclinical evidence suggesting that NK cells may be as effective as T cells in recognizing and killing targets after genetic modification. We will discuss strategies to introduce CARs into both primary NK cells and NK cell lines in an effort to provide antigen specificity, the challenges of manufacturing engineered NK cells, and evidence supporting the effectiveness of this approach from preclinical and early-phase clinical studies using CAR-engineered NK cells. CAR-NK cells hold great promise as a novel cellular immunotherapy against refractory malignancies. Notably, NK cells can provide an "off-the-shelf" product, eliminating the need for a personalized and patient-specific product that plagues current CAR-T cell therapies. The ability to more potently direct NK cell-mediated cytotoxicity against refractory tumors through the expression of CAR is likely to contribute to the recent paradigm shift in cancer treatment.

Keywords: CAR; NK cells; NK expansion; adoptive therapy; cellular therapy; chimeric antigen receptors; genetic engineering; immunotherapy; killer immunoglobulin receptor; natural killer cells.

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Figures

Figure 1
Figure 1
Mechanisms of NK-Mediated Cytotoxicity (A) Spontaneous cytotoxicity. (B) Cytokine release. (C) ADCC. (D) Genetic modification. ADCC, antibody-dependent cell-mediated cytotoxicity; mAb, monoclonal antibody.
See this image and copyright information in PMC

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References

    1. Maude S.L., Frey N., Shaw P.A., Aplenc R., Barrett D.M., Bunin N.J., Chew A., Gonzalez V.E., Zheng Z., Lacey S.F. Chimeric antigen receptor T cells for sustained remissions in leukemia. N. Engl. J. Med. 2014;371:1507–1517. - PMC - PubMed
    1. Davila M.L., Riviere I., Wang X., Bartido S., Park J., Curran K., Chung S.S., Stefanski J., Borquez-Ojeda O., Olszewska M. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci. Transl. Med. 2014;6:224ra25. - PMC - PubMed
    1. Lee D.W., Kochenderfer J.N., Stetler-Stevenson M., Cui Y.K., Delbrook C., Feldman S.A., Fry T.J., Orentas R., Sabatino M., Shah N.N. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385:517–528. - PMC - PubMed
    1. June C.H., Riddell S.R., Schumacher T.N. Adoptive cellular therapy: a race to the finish line. Sci. Transl. Med. 2015;7:280ps7. - PubMed
    1. Sadelain M. CAR therapy: the CD19 paradigm. J. Clin. Invest. 2015;125:3392–3400. - PMC - PubMed

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