COMBINATION IMMUNOTHERAPY WITH OK-432, RECOMBINANT GRANULOCYTE-COLONY-STIMULATING FACTOR AND RECOMBINANT INTERLEUKIN-2 FOR HUMAN HEPATOCELLULAR-CARCINOMA

The antitumor effects of immunotherapy using streptococcal preparation s (OK-432), recombinant granulocyte-colony-stimulating factor (rG-CSF) ana recombinant interleukin-2 (rIL-2) were examined for human hepatoc ellular carcinoma (HCC). Following subcutaneous injection of OK-432 (2 KE) and rG-CSF (50-60 mu g), low-dose intratumoral administration of OK-432 (3-12 KE) was performed. Thereafter, 2 x 10(5) JRU of rIL-2 was subcutaneously injected. This therapeutic regimen was repeated twice. Serum a-fetoprotein levels were markedly decreased in three of seven patients with HCC by this treatment. Posttherapeutic histological exam ination revealed that trabecular cords or pseudoglandular arrangements of tumor cells were completely disordered in all cases and that exten sive infiltration of lymphocytes into the tumor stroma was present in five cases. The number of CD4- and CD57-positive cells among tumor-inf iltrating lymphocytes after immunotherapy was significantly higher tha n that in patients without immunotherapy (P <0.01). These findings sug gest that even a small intratumoral injection of OK-432 can induce ext ensive infiltration of helper/inducer and natural killer cells into th e tumor stroma when combined with subcutaneous injection of OK-432, rG -CSF and rIL-2 and that these cells might play important roles in tumo r cytotoxicity.