Cellular Immunotherapy of Cancer: The use of Lymphokine-Activated Natural Killer (LANAK) Cells

Abstract

“Active immunotherapy” of cancer has been defined as the stimulation of the host immune system aimed at rejection of the tumour. In recent years, this has been the principal subject of research in this field. Attempts have been made to either immunise patients with allo-geneic tumour cells, or to increase their immune responses more generally by nonspecific stimulation with, for example, BCG or interferons [1]. These early trials were most often disappointing, with a few exceptions, such as the local use of BCG in the early stage of bladder carcinoma [2]. Recently, the development of clinical trials with IL2, which is a pivotal mediator of the immune system, has led to a renewed interest in active immunotherapy. Indeed, infusions of high-dose IL2 have been shown to induce partial and even complete responses in a substantial proportion (20-30%) of patients with metastatic renal cell carcinoma and melanoma [3]. An additional approach is represented by “adoptive immunotherapy”, i.e., the transfer of immunologically active agents to the patient. Along these lines, one method has been studied extensively in recent years; it is based on the in-vivo infusion of cells displaying in-vitro antitumour cytotoxic activity. In 1980, S. Rosenberg and co-workers at the United States National Cancer Institute showed that the treatment of murine spleno-cytes with supernatants containing IL2 resulted in the generation of cells able to kill a wide variety of fresh tumour targets, but not normal cells [4]. These lymphocytes were termed LAK (Lymphokine Activated Killer) cells. Subsequent studies in various animal models have shown that, under certain conditions, the transfusion of such killer lymphocytes may lead to the regression of established metastases. We shall briefly summarise here the data from these murine experiments, as well as the initial clinical results obtained when the method based on the animal models was tested in humans. We shall then discuss the current problems related to this approach and the potential developments for the future.