EXPERIMENTAL STUDY OF LOCAL IMMUNOCHEMOTHERAPY FOR HEAD AND NECK CANCER

Abstract

The mechanism of induction of antitumor activity by local administration of recombinant interleukin-2 (rIL-2) combined with cisplatin (CDDP) was investigated in order to establish a method of immunochemotherapy against head and neck cancer.
Local administration of r1L-2 had significantly greater inhibitory effects on tumor growth in both Meth A and C26 tumor bearing mice than did systemic administration. The cytotoxic activity of tumor infiltrating lymphocytes (TILs) obtained from C26 tumor bearing mice was studied. Local injection of rIL-2 around the tumor site for 4 days induced augmentation of the cytotoxicity of TILs not only in NK sensitive tumors but also in NK resistant C26 tumors. This phenomenon was not observed in spleen cells. Both negative selection assay and cold target inhibition assay revealed that the effector cells were tumor nonspecific asialoGMl positive activated NK cells.
Additional experiments were performed to determine the effectivenss of combined immuno-chemotherapy using CDDP and rIL-2 in C26 tumor bearing mice. The intraperitoneal administra-tion of CDDP following the local administration of rIL-2 was more effective in suppressing tumor growth and in promoting well-survival than the use of CDDP or rIL-2 alone.
To investigate the mechanism of antitumor activity, the effects of CDDP on the tumor cells and immunological changes were observed in tumor bearing mice. The susceptibility of tumor cells to effector cells was enhanced after in vitro culture with CDDP. In vivo administration of CDDP augmented the cytotoxic activity of effector cells and responsivenss to IL-2 of TIL.
These results suggest that local immunochemotherapy using locally administered rIL-2 com-bined with CDDP may be available as a therapy for head and neck cancers.