CYTOLYTIC EFFECTS OF AUTOLOGOUS LYMPHOKINE-ACTIVATED KILLER-CELLS ON ORGANOTYPIC MULTICELLULAR SPHEROIDS OF GLIOMAS IN-VITRO

Knowledge about lymphokine-activated killer (LAK) cell infiltration an d WC cell cytotoxicity is essential to improve the effectiveness of Wt cell therapy against gliomas. In the present study, organotypic multi cellular spheroids (OMS) of glioma tissue were used as a culture model to study the effects of LAK cells on gliomas. Compared to tumour cell lines and spheroids derived from tumour cell lines, OMS have several advantages with respect to preservation of tumour cell heterogeneity a nd the maintenance of the tumour architecture, e.g. capillaries and ex tracellular matrix. Four glioma specimens, obtained at surgery, were c ultured directly on agarose to form OMS, which were then co-cultured w ith either autologous LAK cells or autologous non-activated peripheral blood lymphocytes (PBLs). After various time periods of co-cultivatio n, the OMS were fixed and examined both histologically and immunocytoc hemically. The present results showed that LAK cells infiltrated the O MS completely within 24h of co-cultivation and severe cellular damage was observed, whereas PBLs infiltrated the OMS poorly and there was on ly marginal cellular damage. The present study indicates that OMS of g liomas provide an experimental model to investigate the infiltration a nd cytotoxicity of Wt cells on glioma tissue in vitro.