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Recombinant Interleukin-2 and Lymphokine-activated Killer Cell Treatment of Advanced Bladder Cancer: Clinical Results and Immunological Effects¹

Department of Tumor Cell Biology, The Fibiger Institute, Danish Cancer Society, Ndr. Frihavnsgade 70, DK-2100 Copenhagen [G. G. H., J. Z] and Departments of Oncology [P. F. G., H. v. d. M.], Urology [K. S., T. H.], and Pathology [C. A.], Helev Hospital, University of Copenhagen, DK-2730, Heriev, Denmark

The purpose of this study was to evaluate the efficacy of treatment with recombinant interleukin-2 (rIL-2) and lymphokine-activated killer cells in patients with advanced bladder cancer and to study the induced changes in the distribution of leukocyte subsets in blood and tumor.

Nine patients with metastatic transitional cell cancer of the bladder were treated with a continuous infusion of rIL-2 combined with lymphocytes stimulated in vitro with rIL-2. None of the patients responded to the therapy despite substantial changes observed in the immunological cells, both in tumor and blood.

The rIL-2 infusion induced migration of leukocytes to the tumors, which was related to increased expression of the adhesion molecule VLA-1 on both peripheral blood mononuclear cells and the endothelial cells of small tumor vessels. Only T-cells, predominately expressing IL-2 receptors, and macrophages infiltrated the tumors. Natural killer cells remained few or absent in the tumors, even though the natural killer cells in peripheral blood were activated by the treatment.

This study shows that the present technique of rIL-2 and lymphokine-activated killer cell therapy is able to induce substantial changes in the immune system of patients with metastatic bladder cancer. However, this treatment did not induce tumor regression, which may be due to the advanced stage of disease.

¹ The project was supported by the Danish Cancer Society (Grants 74-26/89 and 74-26/90) and the Viholm Foundation, Copenhagen, Denmark. G. G. Hermann was the recipient of a fellowship from the NEYE Foundation, Copenhagen, Denmark.

² To whom requests for reprints should be addressed, at Department of Tumor Cell Biology, The Fibiger Institute, Danish Cancer Society, Ndr. Frihavnsgade 70, DK-2100 Copenhagen, Denmark.

Received 4/ 3/91. Accepted 11/ 5/91.

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