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Cytolytic Potential of Peripheral Blood T-Lymphocytes following Adoptive Immunotherapy with Lymphokine-activated Killer Cells and Low-Dose Interleukin 2¹

Departments of Virology [I. Y., G. K.] and Immunology [M. M., K. N.], Medical Institute of Bioregulation, and Department of Surgery II, Faculty of Medicine [T. I., K. S.], Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812, and Department of Chest Surgery, National Kyushu Cancer Center, Notame, Minami-ku, Fukuoka 812 [T. Y.], Japan

In this study, we investigated the cytolytic activity of peripheral blood T-cells (PBT) obtained from nine patients with primary lung cancer treated by surgical adjuvant adoptive immunotherapy (AIT) with lymphokine-activated killer cells and low-dose recombinant interleukin 2 at the time of rebound lymphocytosis (24–48 h after AIT). In eight of nine patients, nonspecific cytotoxicity of peripheral blood lymphocytes significantly increased as compared with that of pre-AIT peripheral blood lymphocytes. However, purified PBT showed much less activity to kill tumor cells although they increased in number and were activated well in terms of increases in the expression of HLA-DR and interleukin 2 receptor. The cytolytic activity of post-AIT PBT was significantly enhanced when they were targeted to Fc receptor-bearing tumor cells (K562 or Daudi) with anti-CD3 (NU-T3) or anti-T-cell receptor (TCR)ß (WT31) monoclonal antibody in all five patients examined. Phenotypically, the targeted cytotoxicity was predominantly mediated by CD8⁺ cells. The results indicated that in vivo-activated PBT by AIT could not exhibit direct cytotoxicity, but they acquired cytolytic potential, the effect of which was expressed by targeting to tumor cells.

¹ This work was partially supported by Grant 02557049 from the Ministry of Education, Science and Culture and by a Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare, Japan.

² To whom requests for reprints should be addressed.

³ On leave of absence from Japan Synthetic Rubber Co., Ltd.

Received 9/20/90. Accepted 12/13/90.