| 1995 | Folia Pharm. Univ. Carol. 19 | Pag. 45—55 |
Petr Jílek1 (jilek@faf.cuni.cz), Jan Krejsek2, Milana Kšírová1
1Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové
22nd Department of Medicine, School of Medicine, Charles University, Hradec Králové
Lymphokine activated cells (LAK) are promissing agent in adoptive immunotherapy of tumors. Immunotherapy at all is based on the stimulation of effectors of anticancer immunity. Some cytokines have good stimulatory activity in this point of wiev, but, when applicated systemically, they exhibit severe side effects. Cytotoxic cells can be stimulated in vitro (after removing from patient’s blood) and then reinfused back with reduced doses of cytokines and with lower risk of toxicity. Many different procedures for preparation of LAK cells have been developed, but the basic principles are generally identical:
The peripheral blood mononuclear cells (PBMC) are obtained by leukapheresis and then used for the generation of LAK cells. Recombinant IL-2 (rIL-2) have been usually used for the stimulation of precursor cells. Various cultivation media are used, mainly it is RPMI 1640 in different modifications with or without serum. Also other serumfree media are recommended. The optimal conditions for the cultivation of LAK cells are: plastic bags, atmosphere with 5% carbondioxide, temperature 37°C, time of incubation 3—5 days. It is also possible to cultivate LAK cells for the longer period (till 14 days) in highly effective systems. The sufficient amount of LAK cells (1010—1011) is necessary for the achievement of the clinical effect. Regarding these data, the adoptive immunotherapy is predestined mainly for the patients without previous cytoreductive therapy. The assessment of cytotoxic activity in vitro, cell viability and sterility before re-infusion is obligatory.
The therapeutic regimens include the application of IL-2 several days before the leukapheresis. The higher amount of precursors of LAK cells is obtainable after the cessation of IL-2. The leukaphereses are performed on the 5 consequent days and precursors of LAK cells are cultivated for 35 days. LAK cells are re-infused to the patient together with rIL-2, which is necessary for in vivo proliferation and lifetime prolongation of transferred cells (LAK/IL-2 therapy).
The best results of LAK/IL-2 therapy have been achieved in patients suffering from renal cell carcinoma and malignant melanoma.