Chapter Twelve - Development and testing of NK cell lines

Abstract

Infusion of enriched natural killer (NK) cell preparations have now become a therapeutic possibility with the advent of magnetic columns that can deplete unwanted cells and enrich NK cells. The “self” major histocompatibility complex (MHC) antigens expressed by the cancer cells prevent their recognition by autologous NK cells and in fact inactivate them through the KIR receptor mechanism, in spite of the presence of activating ligands for NKG2D. Legitimate NK cell lines are defined by the expression of CD56 and being negative for CD3 expression and T-cell receptor rearrangement with the exception of a truncated TCRβ chain observed in some cells. Most of the NK cell lines were established from patients with NK lymphoma or large granular lymphocytes (LGL) leukemia and the majority are Epstein–Barr Virus (EBV) positive, which probably contributed to their clonal outgrowth. The NK-92 cell line was initially EBV negative, but over time acquired the virus although no active virions are produced. These cell lines have become useful to investigators to study the biology of NK cells and NK lymphomas/leukemias. The only NK cell line that has undergone extensive preclinical development and has completed phase I clinical trials is NK-92. The cell line was established in 1992 from a patient with NK cell lymphoma, has been well characterized and has been taken through phase I trials in the United States and Europe. The consistently high cytotoxic activity of NK-92 cells is due to the fact that they do not express any currently known inhibitory KIR. When NK-92 cells are transfected with KIR, they lose their cytolytic activity, further supporting the importance of KIR in NK– tumor target cell interaction.