EFFICACY OF IN-VITRO SENSITIZED CELLS GENERATED BY IN-VIVO PRIMING WITH OK-432 FOR ADOPTIVE IMMUNOTHERAPY OF THE POORLY IMMUNOGENIC B16-BL6MELANOMA

We investigated the efficacy of the streptococcal preparation OK-432 a s an adjuvant for in vivo priming in induction of sensitized cells for adoptive immunotherapy of the poorly immunogenic Bl6-BL6 (BL6) melano ma. C57BL/6 (B6) mice were immunized subcutaneously (s.c.) with 3 x 10 (6) viable BL6 tumor cells admired with various doses of OK-432 rangin g from 1 to 100 mu g in the foot-pad. Draining popliteal lymph nodes ( LNs) were harvested 7 days after immunization and LN cells were furthe r sensitized with irradiated tumor cells in the presence of 60-300 IU/ ml of IL-2 for 11 days. These in vitro sensitized (IVS) cells (2 x 10( 6)) were transferred intravenously (i.v.) to B6 mice bearing 4-day pul monary metastases established by i.v. injection of 2-4 x 10(5) viable BL6 cells. The mice were also received intraperitoneally (i.p.) 4 x 10 (4) IU/day of IL-2 for 4 days after adoptive transfer. Transfer of IVS cells from mice immunized by s.c. injection of tumor cells admired wi th 10 mu g of OK-432 significantly reduced the numbers of BL6 pulmonar y metastases compared with that of control IVS cells without the admin istration of OK-432 (P = 0.003). These effective IVS cells also signif icantly prolonged the survival of treated animals (P = 0.003). Functio nal IVS cells required in vitro stimulation with tumor cells. However, addition of OK-432 in the vaccine resulted in no enhancement of in vi tro cytotoxicity and no characteristic change of phenotype of IVS cell s. These results suggest that in vivo priming of OK-432 facilitates th e sensitization of tumor-reactive T-cells. The procedure of in vivo pr iming with OK-432 may be beneficial in the adoptive immunotherapy of m elanoma. Copyright (C) 1996 International Society for Immunopharmacolo gy