picibanil and Plasmacytoma

BALB/c mice inoculated IP with a syngeneic plasmacytoma MOPC104E were treated with a combination of a streptococcal preparation, OK-432 (1 KE, 0.1 mg/mouse), low-dose of cyclophosphamide (CPA, 1 mg/kg) and adoptive transfer of tumor-bearer-spleen cells (2 x 10(7) cells) cultured with IL2 and sonicated tumor extract (adoptive immunotherapy; AIT). The consecutive protocol of OK-432 (day 8, 9 post inoculation) - CPA (day 10) - AIT (day 11) was the most effective. Rate of complete remission was highest when recombinant (r-) IL2 was injected to the mice after AIT. Moreover, another bacterial preparation, Nocardia rubra cell wall skeleton and another low-dose chemotherapy, Mitomycin C could be used successfully instead of OK-432 or CPA. Transfer test of intraperitoneal cells (tumor cells plus host cells) of mice on day 11 post inoculation (on the day of AIT) revealed that OK-432 augmented the susceptibility of peritoneal cells to cultured lymphocytes in inhibition of transplantability, and that CPA after OK-432 augmented the anti-tumor effect of tumor-bearer-spleen cells which act synergistically with cultured lymphocytes. This therapy schedule seems to be the best model to augment the effect of AIT with minimal side effect.

Topics: Animals; Biological Products; Combined Modality Therapy; Cyclophosphamide; Immunization, Passive; Interleukin-2; Killer Cells, Lymphokine-Activated; Male; Mice; Mice, Inbred BALB C; Peritoneal Cavity; Picibanil; Plasmacytoma; Spleen

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.

Topics: Animals; Biological Products; Fibrosarcoma; Immunization, Passive; Interleukin-2; Killer Cells, Natural; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Transplantation; Neoplasms, Experimental; Picibanil; Plasmacytoma; Thymoma

Topics: Animals; Biological Products; Cells, Cultured; DNA, Neoplasm; Immunotherapy; Interleukin-2; Liver Neoplasms, Experimental; Lymphocytes; Male; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Picibanil; Plasmacytoma; Spleen