Cytotoxic effects of human alpha interferon against human renal cancer cell line (KU-2).

Reactivity of natural killer (NK) cells to an established human renal cancer cell line (KU-2) was determined by cellular immunoadsorbant tech nique, utilizing human leukemia cell line (CCRF-CEM) which is highly sensi tive to NK cells. The influence of human alpha interferon (HuIFN-ƒ¿) on NK activity against KU-2 cells was also determined by microcytotoxicity assay. Percent cytotoxicity increased 84%, 52% and 59% in non E-rosette forming (non ERF) lymphocytes, ERF lymphocytes and unseparated peri pheral blood lymphocytes (PBL), respectively, under effector cells/target cells ratio being 25/1 and preincubation with 150 IU/ml HuIFN-ƒ¿. The re sults indicated that more marked influence of HuIFN-ƒ¿ upon non ERF lym phocytes was expected than ERF lymphocytes. Identification of the effector lymphocytes under influence of HuIFN-ƒ¿ was undertaken by scanning electron microscopic observation. Lymphocytes characterized by relatively smooth surface and short microvilli were observed to be adherent to the surface of the KU-2 cells showing destruction of their morphological integrity. To determine the direct cytotoxic effects, the KU-2 cells were exposed to HuIFN-ƒ¿. When exposed to 501U/ml HuIFN-ƒ¿, cellular doubling time extended from 23 hrs to 38 hrs. With more than 200 IU/ml, the growth was acceptably inhibited and no dose dependent effect on the growth curves was nhserved in large dose series. From the results of in vitro studies, it was determined that both NK activation and direct inhibitory mechanisms were involved in the growth inhibitory effect of HuIFN-ƒ¿ against KU-2 cells. HuIFN-ƒ¿ was suggested to play an important role in a multimodal treatment of human renal cell carcinoma.