Studies on Treatment Effects and Prognoses of Adoptive Immunotherapy of Cancer Patients by using autologous and allogeneic lymphocytes.

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Culture of peripheral blood mononuclear cells (PBMC) with a heat and penicillin-treated streptococcal preparation, OK-432, has induced effector cells which have both cell-mediated and cytokine-mediated antitumor activities. We performed locoregional adoptive immunotherapy (AIT) with OK-432-activated PBMC (OKMC) in head and neck cancer patients as a part of preoperative treatment. In the present study we evaluated the correlation of tumor mononuclear cell infiltration and patient's prognosis. The AIT group (10 cases) was more abundant in infiltrating T cells (UCHL-1+) in tumor tissue than those of the non-AIT group (10 cases). There were three recurrences out of 10 cases of AIT group, in which a small number of OKMC was transferred and had much less T cell infiltration of the tumor parenchyma.Tumor tissues were surgically excised and therapeutic effect was examined histologically. In AIT group, focal necrosis of cancer tissue was observed at the site of OKMC injection especially at the portion of massive infiltration of mononuclear cells. These cell death was characteristic of apoptosis as examined by HE and immunohistochemical staining with anti-Le^y antibody. Various kind of cytokine mRNAs including IL-1, TNFalpha, IL-6, IFNgamma, IL-2, IL-4 were also detected in the tumor burden by RT-PCR technique. The IL-1 and IL-2 mRNA were detected in almost all of the tumor tissue, but IFNgamma was found only in 50% of these cases. Furthermore, tumor tissue which lack the IFNgamma message was unequivocally expressed immunosuppressive cytokine IL-10. The IFNgammamRNA was reappeared after the AIT in the tumor tissue which could not be detected its message before AIT.The above mentioned phenomena were presumed to be direct effect of AIT.Thus, it is considered that local administration of OKMC could be one of the most feasible BRM therapies in head and neck cancers.