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In Vivo Induction of the Lymphokine-activated Killer Phenomenon: Interleukin 2-dependent Human Non-Major Histocompatibility Complex-restricted Cytotoxicity Generated in Vivo during Administration of Human Recombinant Interleukin 2¹

Departments of Human Oncology [J. A. H., P. C. K., G. W-H., N. R., K. H. M., B. S., D. M., J. B., R. B., P. M. S.], Statistics [B. S.], Pediatrics [P. M. S.], and Genetics [P. M. S.], University of Wisconsin, Madison, Wisconsin 53792

The availability of purified human recombinant interleukin 2 (IL-2) has enabled clinical trials to test its in vivo effects. We report here the immunological effects of 7 consecutive days of IL-2 treatment given to 25 patients with cancer in a clinical Phase I study. Peripheral blood lymphocytes obtained from patients following therapy with IL-2 had enhanced proliferative responses to IL-2 and enhanced direct cytotoxic activity on K562 target cells. This lytic activity was further augmented by the addition of IL-2 during the ⁵¹Cr release assay. Fresh peripheral blood lymphocytes from some patients who had just completed treatment at the higher IL-2 dose levels were able to kill both the natural killer-resistant Daudi cell line and fresh tumor cells while pretreatment samples and peripheral blood lymphocytes from healthy controls were not. This lytic activity was best detected when IL-2 was present in the in vitro effector assay. These results demonstrate that the administration of IL-2 to patients with cancer induces a population of effector cells able to directly destroy natural killer-resistant target cells, when assayed in the presence of IL-2.

¹ This research was supported by Grants NIH-CA 32685-5, American Cancer Society CH-237B, and Contract N01-CM 47669: B85-001 of the National Cancer Institute Biologic Response Modifiers Program.

² To whom requests for reprints should be addressed, at K4/450 UWCCC, 600 Highland Avenue, Madison, WI 53792.

Received 6/ 9/87. Revised 10/ 1/87. Revised 12/14/87. Accepted 12/28/87.

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