Immunotherapy for cancer: the use of lymphokine activated killer (LAK) cells.

Abstract

The inability of the tumour bearing host to mount an immune response sufficient for the lysis of significant numbers of tumour cells has long been the stumbling block for those interested in the immunotherapy of cancer. Therapeutic approaches designed to immunise the host against putative tumour antigens have been generally unsuccessful.12 Attempts to boost immune responses with general immunostimulants have failed, largely because of their lack of specificity and the general paucity of immune responses produced in the tumour bearing host.'2 The development of 'passive' immunotherapy whereby previously sensitised antibodies or cells ('adoptive' immunotherapy)l5 are capable of mediating antitumour responses on transfer to a host, represented an attractive alternative to previous therapies for several reasons. This ready-made approach would overcome the problems of host immunoincompetence, offer high specificity and could be combined with other therapeutic modalities. 1-5 One handicap was the relative inability to generate large numbers of sensitised, preferably syngeneic cells, suitable for transfer. '-5 The first step forward came in 1980 when Rosenberg and colleagues described a novel method for generating large numbers of lymphoid cells which, after exposure to interleukin-2, were capable of lysing fresh, non-cultured primary and metastatic cancer cells.6 These lymphokine activated killer (LAK) cells are functionally distinct from the population of natural killer cells, because they can lyse tumour cells previously shown to be resistant to natural killer activity.3'0 Furthermore, they are specific for tumour cells and have little, if any, activity against normal cells.> Killer activity is not Major Histocompatibility Complex restricted being maintained against non-immunogenic, allogeneic as well as syngeneic tumours.3 The next step came in 1983 when Taniguchi and colleagues, using recombinant techniques, cloned the gene for interleukin-2 in a (JURKAT) cell line.9 Shortly afterwards Rosenberg et al produced interleukin 2 from E coli as well as the JURKAT cell line.'0 These manoeuvres allowed large quantities of pure product to be used. Intravenous administration of large numbers of LAK cells in combination with interleukin-2 (alone neither is very effective) was shown to decrease the number and size of a variety of secondary tumours in the liver and lungs in several murine and guinea pig tumour model systems`I: similar results have been reported with preliminary studies in man.'2 Eleven of 25 patients with various types of pulmonary or hepatic metastases exhibited objective remission (a greater than 50% reduction in tumour volume) after one to three cycles of therapy given over two to …

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@article{Fagan1987ImmunotherapyFC, title={Immunotherapy for cancer: the use of lymphokine activated killer (LAK) cells.}, author={Elizabeth A. Fagan and Adrian L. W. F. Eddleston}, journal={Gut}, year={1987}, volume={28 2}, pages={113-6} }