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 Cal mette-Guerin (BCC) has become the therapy of choice in superficial bla dder cancer recurrences. This effect could be correlated in-vitro by e ffectively activating peripheral blood mononuclear cells with BCG to c ytotoxicity 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-pre senting monocytes and CD4(+) T-lymphocytes. Recognition and killing of target cells is MHC-unrestricted. In experiments presented here, we c ompared this unique cytotoxic population with the better known cell po pulation of established clinical relevance, the lymphokine-activated k iller, or ''LAK'' cells, with regard to their cytotoxic activity again st urothelial cells from malignant and, most importantly, benign origi n. A striking difference between both effector cell populations was th at BAK cells, in contrast to LAK cells, did not affect normal urotheli al cells. This suggests an inherent ability of BAK cells to distinguis h between malignant and benign. Furthermore, cold target inhibition as says led us to conclude that BAK cells represent a homogeneous cell po pulation, whereas LAK cells obviously consist of at least two subpopul ations with differential recognition and killing characteristics.