Establishment of a murine leukemia L1210-specific T-cell clone displaying novel in vivo anti-tumor activity.
The murine leukemia L1210-specific cytotoxic T-cell clone K7 was established by repeated antigenic stimulation of spleen cells of L1210-immune CD2F1 mice in long-term culture. K7 possessed L1210-specific cytolytic activity detectable by the 51Cr-release test, but lost its cytolytic activity about 100 days after initiation of culture (designated as clone K7L). Clone K7L retained its L1210-specific tumor-growth-inhibitory activity independently of culture supplementation with IL-2. K7L possessed the cell-surface antigenic phenotype of cytotoxic T cells, Thy-1+, Lyt-1-, Lyt-2+. This clone K7L displayed surprisingly strong activity in specifically inhibiting in vivo tumor growth of L1210 by day 5 in the peritoneal cavity of CD2F1 mice when injected together with 10(5) tumor cells (more than 90% inhibition at E/T = 5), and prolonged survival times of most of the mice for more than 60 days, whereas control mice inoculated with L1210 alone died on day 9-17. This unique in vivo anti-tumor activity was not correlated to the in vitro cytolytic activity. Nevertheless, bystander inhibitory effect on the growth of third-party tumor cells (P388) was not seen in mice injected with a mixture of L1210 and P388 together with K7L, suggesting that K7L inhibited L1210 growth by direct cell-to-cell interaction. Host cells such as X-irradiation (800R)-sensitive lymphocytes and Carrageenan-sensitive macrophages were not involved in the early growth inhibition of L1210 by K7L.
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D002455:Cell Division; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005260:Female; D007518:Isoantibodies / Q000276:immunology; D007939:Leukemia L1210 / Q000276:immunology*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000954:Antigens, Surface; D007518:Isoantibodies; C029805:Lyt antibodies