Lymphokine-activated killer (LAK) cell purging of bone marrow

Abstract

The in vitro incubation of NK cells with the lymphokine IL-2 stimulates the development of a population of activated cytotoxic lymphocytes (LAK cells). These activated cells have the capacity to recognize and kill a wide range of neoplastic cells. The cytotoxic activity of LAK cells does not appear to be directed against normal, non-neoplastic cells and we have recently examined the potential for using LAK cells as a method of purging bone marrow for autologous transplantation in patients with widespread neoplastic diseases. We have utilized an experimental system consisting of the incubation of LAK cells from inbred F344 rats and normal bone marrow and demonstrated that this procedure does not interfere with the ability of the treated bone marrow to reconstitute lethally-conditioned recipients. The frequency and rate of reconstitution is the same in treatment and control groups, including incubation periods that extend up to 18 hours. When RNK-16 leukemia cell line (a spontaneous large granular lymphocyte leukemia that is syngeneic to the F344 strain) is added to the incubation mixture, the LAK cells have the ability in vitro to recognize the neoplastic cells and prevent the transmission of the leukemia to naive animals following bone marrow transplantation. As expected from the in vitro LAK cytotoxic activity, these activated cells are capable of recognizing and eliminating a variety of neoplasms. To date we have tested three different hematopoietic tumor lines derived from the F344 strain and one that was induced in an unrelated BN strain. In each case, the F344 LAK cells demonstrated an ability to prevent the transmission of a fatal leukemia and significantly prolong the survival of animals that had received larger numbers of neoplastic cells. The tumor lines examined included the RNK-16 line (NK cells), the Dunning leukemia (monocyte-lymphoblastic leukemia), a T-lymphocyte lymphoma and the acute myelogenous leukemia of BN rats (BN AML). Comparison of the results of these purging experiments to those seen when control animals are injected with graded doses of the individual tumors indicate that the LAK cells are eliminating approximately 2-3 logs of neoplastic cells. The ability of LAK cells to kill a wide range of tumors without damage to the ability of the recipient stem cells to reconstitute the bone marrow may allow for an important application for this type of purging technique in patients with neoplasms for which specific immunological or chemical therapies do not exist.