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Induction of High-Grade Tumor-specific Immunity in a Host Using a Cytotoxic T-Lymphocyte Clone Specific for a Stable Tumor Antigen on Murine Leukemia L1210¹

Departments of Immunology [S. M. J. R., I. N.] and Clinical Laboratory Medicine [K. K.], Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466, Japan, and Department of Medical Technology, Nagoya University College of Medical Technology, Nagoya 461, Japan [F. N.]

T-cell clone K4L, the cell surface phenotypes of which were Thy-1⁺, Lyt-1^-, Lyt-2⁺, and L3T4^-, was established from the spleen cells of a murine leukemia L1210-immune mouse. Clone K4L was specific for antigen B on L1210, and this antigen was different from antigen A for which the previously reported T-cell clone K7L was specific. K4L possessed cytotoxicity and tumor growth-inhibitory activity against both L1210 and antigen A loss variant, L1210-K7L^-, but not against syngeneic tumor P388 or L5178Y. Previously we showed that antigen A was lost frequently for generation of antigen loss variants. In contrast, antigen B was barely found to be lost. When mice were inoculated with L1210 plus a moderate dose of K4L, the tumor grew after initial suppression but this newly emerging tumor was K4L sensitive and was ultimately rejected. The mice initially given L1210 plus K4L attained a high-grade tumor-specific immunity for rejecting the subsequently challenged high-dose (10⁷ cells) L1210. This immunity did not involve any bystander antitumor activity against the third party P388 lymphoma that was injected together with L1210 but accompanied the increase in the L1210-specific cytotoxic T-lymphocyte activity. Evidence was provided that the live L1210, the outgrowth of which was inhibited by K4L, induced an effective immune response of radiation-sensitive host lymphocytes including L3T4⁺ helper T-cells. Taken together, our results show a novel strategy for inducing high-grade host-dependent antitumor immunity by use of a cytotoxic T-lymphocyte clone specific for a stable tumor-specific transplantation antigen.

¹ This research was supported in part by The Ishida Foundation and by Aichi Cancer Research Foundation.

² To whom requests for reprints should be addressed.

Received 2/12/88. Revised 7/ 1/88. Accepted 8/16/88.