Cell surface recognition determinants involved in triggering the lymphokine activated killer cell phenomenon: enhanced killing of modified "anti-self" targets by varying LAK culture conditions

Abstract

Lymphokine activated killer (LAK) cells were first described by Rosenberg, et al in the early 1980s. In attempting to grow lymphoid cells infiltrating solid tumors, they discovered that such cells, when incubated with the cytokine Interleukin-2 (IL-2), gained the ability to lyse a wide range of auto and allogeneic tumors while sparing normal non-malignant cells. A number of preliminary clinical trials have shown that when LAK cells and IL-2 are infused into patients with end-stage metastatic cancer, impressive tumor regression, and in some cases tumor eradication, can occur, albeit in the face of significant toxicity. Little is understood about how a potential target cell "signals" its malignant character to a LAK cell. Our approach to this problem has been to investigate the role of the absence or modification of certain self antigens which seem to provide LAK cells with a lysis trigger. By manipulating the culture conditions in which the killer cells are grown, we provide evidence that different subsets of LAK cells may lyse different types of tumor targets. These differences may be important in fine-tuning LAK treatment that is more active at the tumor site in vivo and less toxic to patients.