Adoptive immunotherapy in tumor-bearing mice with OK-432-induced killer cells.
Murine spleen cells cultured for 3 or more days in medium with streptococcal preparation OK-432 became cytotoxic in vitro against several allogeneic and syngeneic tumor cells. These cytotoxic cells were designated OK-432-induced killer (OIK) cells. This study examined the in vivo antitumor efficacy of OIK cells in adoptive immuno- and immunochemo-therapy in mice bearing syngeneic tumors, such as EL-4 lymphoma, Meth-A fibrosarcoma, and MOPC-31C plasmacytoma. OIK cells neutralized these tumor cells, as shown by Winn-type tests, and the cell transfer prolonged the survival of mice inoculated intraperitoneally (ip) with EL-4 or Meth-A cells. Concomitant administration of OK-432 plus recombinant interleukin 2 (rIL-2) significantly improved the therapeutic efficacy of the transferred OIK cells. In mice inoculated with 1 x 10(4) EL-4 cells, chemoimmunotherapy consisting of ip administration of 200 mg/kg cyclophosphamide on day 3 followed by treatment with OIK cell (1 x 10(7)) transfer and with OK-432 (50 KE/kg) plus rIL-2 (50 units/mouse) 6 hr later and on day 6, prolonged the survival. Therefore, the immunotherapy with OIK-cell transfer followed by administration of OK-432 and rIL-2 may be clinically useful as an adjunct of cytoreductive chemotherapy for cancer.
Ujiie
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Department of Experimental Therapeutics, Kanazawa University, Japan.
D000818:Animals; D001688:Biological Products / Q000276:immunology*; D005354:Fibrosarcoma / Q000628:therapy; D007116:Immunization, Passive; D007376:Interleukin-2 / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000628:therapy*; D010844:Picibanil / Q000276:immunology*; D010954:Plasmacytoma / Q000628:therapy; D013945:Thymoma / Q000628:therapy
D001688:Biological Products; D007376:Interleukin-2; D010844:Picibanil