Cellular immunotherapy of malignancies using the clonal natural killer cell line NK-92

For years activated natural killer (A-NK) cells have been explored with res pect to their efficacy in anticancer therapy, but, except for some anectdot al reports, no clear clinical benefit has been shown. However, as the under standing about the interactions of NK cells and tumor cells advances, the u se of A-NK cells might be revisited with more sophisticated approaches that pay tribute to mechanisms which allow tumor cells to escape immune surveil lance. Here the highly cytotoxic NK cell line NK-92 seems to be an attracti ve alternative for use in adoptive immunotherapy, because it was shown to e xhibit substantial antitumor activity against a wide range of malignancies in vitro as well as in xenografted SCID mice. NK-92 cells are characterized by an almost complete lack of killer cell immunglobulin-like receptors (KI Rs) yet conserved ability to perforin and granzyme B-mediated cytolytic act ivity, which make them unique among the few established NK and T cell-like cell lines. NK-92 is the only natural killer cell line that has entered cli nical trials. Here we discuss the current status of development of this cel l line for adoptive immunotherapy (AIT) of malignancies and review our firs t clinical experience in patients with advanced cancer who have received re peated transfusions of irradiated NK-92 in a phase I/II trial. Also we disc uss issues that address safety aspects of immunotherapy with clonal cell li nes and describe further manipulations, which hold the potential of signifi cantly improving the clinical outcome of AIT with NK-92.