[Effect of combined immunotherapy using two different BRMs; OK-432 and IL-2-cultured lymphocytes].
We have developed an adoptive immunotherapy (AIT) system using syngeneic tumor-bearer-spleen cells cultured with interleukin-2 (IL-2) and soluble tumor extract. The therapeutic effect of the AIT was significantly augmented by in vivo local preadministration of a streptococcal preparation, OK-432. The previous report demonstrated a mechanism in which OK-432 augments the effect of AIT. That is, OK-432 induces IL-2 in vivo and prolongs the in vivo life span of cultured, IL-2-dependent lymphocytes (CL). This paper describes another mechanism, that is, the synergism between CL and OK-432-induced host lymphocytes. Fresh spleen cells (FSC) obtained from mice in complete remission after chemotherapy (cyclophosphamide, 100 mg/kg) showed a clear synergistic anti-tumor effect on CL, when both were injected i.p. into MOPC104E-bearing BALB/c mice which had been inoculated i.p. with 1 X 10(5) tumor cells 5 days previously. The effect was greatest when the FSC: CL ratio was 4:1, whereas the administration of either FSC or CL alone had little effect. The effector population of CL that exhibited synergism on FSC was Lyt 2+, cytotoxic T cells. FSC and CL both needed a tumor-specific combination. In addition, OK-432-induced tumor-infiltrating, intraperitoneal lymphocytes had a similar synergistic effect on CL as assessed by the transplantability of intraperitoneal cells. Probably because of this mechanism, OK-432 showed a much higher augmenting effect on AIT using CL than in vivo administration of IL-2. This therapy system using OK-432 and CL is a proper model which, through combined use of different, correlated BRMs, may bring a great effect whereas the effect of single BRM is weak.
D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology; D001688:Biological Products / Q000627:therapeutic use*; D006801:Humans; D007116:Immunization, Passive; D007376:Interleukin-2 / Q000627:therapeutic use*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000628:therapy*; D010844:Picibanil / Q000627:therapeutic use*
D000912:Antibodies, Neoplasm; D001688:Biological Products; D007376:Interleukin-2; D010844:Picibanil