NK cells are essential for effective BCG immunotherapy

Adjuvant intravesical bacillus Carmette-Guerin (BCG) therapy is a well esta blished and successful adjuvant immunotherapy in the treatment of superfici al bladder cancer. Although the function of natural killer (NK) cells in ot her immunotherapeutic regimens (e.g,, lymphokine-activated killer [LAK] cel l or interleukin-2 [IL-2] therapy) has been established, the contribution o f NK cells to effective BCG immunotherapy is not clear. We used a human in vitro system to analyze the role of NK cells in BCG-induced cellular cytoto xicity, After stimulation of mononuclear cells with BCG for 7 days, these B CG-activated killer (BAK) cells displayed substantial cytotoxicity against bladder tumor cells, Magnetic depletion experiments and fluorescence activa ted cell sorting revealed that NK cells were the major effector cell popula tion. To address NK cell function in vivo, we studied a syngeneic orthotopi c murine bladder cancer model and compared BCC immunotherapy in C57BL/6 wil d-type mice, NK-deficient beige mice and mice treated with anti-NKI,I monoc lonal antibody. Four weekly instillations of viable BCG significantly prolo nged survival in wild-type mice compared with control mice treated with sol vent alone, In contrast, BCG therapy was completely ineffective in NK-defic ient beige mice and in mice treated with anti-NKI,I monoclonal antibody. Th ese findings suggest a key role for NK cells during BCG immunotherapy. (C) 2001 Wiley-Liss, Inc.