BCG-activated killer cells: In-vitro study of specific recognition and killing mechanisms of intravesical immune therapy with BCG

Adjuvant intravesical instillation of viable mycobacteria Bacillus Calmette-Guerin (BCC) has become the therapy of choice in superficial bladder cancer recurrences. This effect could be correlated in-vitro by effectively activating peripheral blood mononuclear cells with BCG to cytotoxicity towards bladder cancer cells from permanent cells lines or freshly prepared specimen. The induction of these CD8(+) CD56(+), so-called "BCG-activated killer" (BAK) cells is mediated by antigen-presenting monocytes and CD4(+) T-lymphocytes. Recognition and killing of target cells is MHC-unrestricted. In experiments presented here, we compared this unique cytotoxic population with the better known cell population of established clinical relevance, the lymphokine-activated killer, or "LAK" cells, with regard to their cytotoxic activity against urothelial cells from malignant and, most importantly, benign origin. A striking difference between both effector cell populations was that BAK cells, in contrast to LAK cells, did not affect normal urothelial cells. This suggests an inherent ability of BAK cells to distinguish between malignant and benign. Furthermore, cold target inhibition assays led us to conclude that BAK cells represent a homogeneous cell population, whereas LAK cells obviously consist of at least two subpopulations with differential recognition and killing characteristics.