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Immunotherapy of Mice with a Large Burden of Disseminated Lymphoma with Low-Dose Interleukin 2

Department of Pathology, University Hospital Utrecht, P.O. Box 85500 HP. H04.312, 3508 GA Utrecht [R. A. M., H. F. J. D., W. D. O.] and National Institute of Public Health and Environmental Hygiene, P.O. Box 1, Bilthoven [W. H. D. J.], The Netherlands

Successful immunotherapy with recombinant interleukin 2 (rIL-2) of mice bearing a large burden of lymphokine-activated killer-resistant disseminated SL2 lymphoma is described. When mice were challenged i.p. with 2 x 10⁴ SL2 cells on day 0 and treated with daily i.p. injections of 5,000 units rIL-2 on days 3–7, no therapeutic effect was observed. However after treatment with daily IL-2 injections on day 10–14, 25% of the mice survived. Ten days after this tumor challenge more than 10⁸ SL2 cells were present growing as ascitic tumor. On day 10, SL2 cells were also present as solid tumor in the greater omentum and as metastases in lungs and liver. Surviving mice were able to reject a second challenge with SL2 cells given on day 60. A second challenge with P815, another DBA/2 tumor, resulted in death of the mice due to tumor development. This finding is of particular importance as the SL2 cells are resistant to lymphokine-activated killer activity.

Thus local (i.p.) injection of low dose rIL-2 can cause the systemic rejection of advanced and metastasized cancer. Our data indicate that IL-2 can strongly enhance a specific immune reaction against tumor cells.

¹ To whom requests for reprints should be addressed, at University Hospital Utrecht, Department of Pathology, P. O. Box 85500 HP. H04.312, 3508 GA Utrecht, The Netherlands.

Received 2/15/89. Revised 8/ 1/89. Revised 9/ 7/89. Accepted 9/14/89.