Cell therapy with preimmunized effector cells mismatched for minor histocompatible antigens in the treatment of a murine mammary carcinoma

Cell therapy with allogeneic donor cells mismatched for minor histocompatib le (MiHC) antigens was applied to a murine mammary carcinoma (4T1) model to test the feasibility of graft versus tumor (GVT) effect against metastatic epithelial tumor cells. BALB/c mice bearing a 4T1 tumor of BALB/c origin w ere given syngeneic or MiHC-mismatched splenocytes. GVT effects were determ ined in secondary recipients of adoptively transferred lung cells derived f rom primary hosts who had previously been inoculated intravenously with 4T1 cells, and injected with one of the following: 1) naive BALB/c splenocytes 2) naive DBA/2 splenocytes. 3) 4T1-immune DBA/2 splenocytes, or 4) DBA/2 s plenocytes: immunized with host-derived BABL/c spleen cells. Naive DBA/2 sp lenocytes inhibited tumor growth only slightly and only slightly prolonged the survival of secondary recipients, in comparison with fully matched tumo r/host BALB/c spleen cells. An efficient GVT reaction was demonstrated in v itro and in vivo with MiHC-mismatched DBA/2 splenocytes fi om mice presensi tized by multiple injections of irradiated tumor or BALB/c-derived spleen c ells. All 30 mice adoptively inoculated with lung cells from primary hosts that had previously been treated with these presensitized effector cells we re tumor free for >250 days. Secondary recipients inoculated with lung cell s from mice given naive BALB/c or DBA/2 spleen cells died of metastatic tum ors within 33 to 46 days. These results suggest that preimmunized donor cel ls represent an effective tool against metastatic disease; hence, the next goal should be to control graft versus-host disease while exploiting the GV T potential.