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Critical Reviews™ in Oncogenesis

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ISSN Imprimir: 0893-9675

ISSN En Línea: 2162-6448

SJR: 0.395 SNIP: 0.322 CiteScore™:: 2.5 H-Index: 54

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NK Cells in Therapy of Cancer

Volumen 19, Edición 1-2, 2014, pp. 133-141
DOI: 10.1615/CritRevOncog.2014011091
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Veronika Bachanova
Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN
Jeffrey S. Miller
Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN

SINOPSIS

Natural killer (NK) cells recognize targets stressed by malignant transformation or infection and can be long-lived. They become educated by interacting with major histocompatibility antigen (MHC) class I molecules to gain function to kill targets and produce cytokines. In the clinic, haploidentical NK cells can be adoptively transferred to treat cancer. Persistence and in vivo expansion of NK cells depends on lymphodepleting chemotherapy to make space and induce release of endogenous IL-15. In vivo expansion is also enhanced by cytokine administration but IL-2 has the down side of stimulating CD25hi regulatory T cells (Tregs). Other limitations to NK-cell therapy include poor in vivo survival and lack of specificity. Bispecific or trispecific killer engagers that target CD16 on NK cells to enhance recognition of tumor antigens, and desintegrin and metalloproteinase 17 (ADAM17) inhibition that prevents CD16 shedding after NK-cell activation should promote enhanced killing of cancer with specificity. These are exciting times; more than 35 years after NK cells were initially described, we are exploiting their capacity for clinical therapy.

PALABRAS CLAVE: NK cells, adoptive transfer, allogeneic NK cells, cancer
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