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Vaccination with Tumor Cells Engineered to Secrete Interleukin 2-Immunoglobulin G Fusion Protein Induces Tumor Rejection¹

Institute of Immunology [S. B-P., H. v. B., D. U., T. P.], Departments of Ophthalmology [J. W.], Internal Medicine [M. N.], and Urology [H. K.], University Hospital Benjamin Franklin, Free University, 12200 Berlin, Germany; Department of Dermatology Charité, Humboldt University, Berlin, Germany [R. R. and R. P.]; and Department of Internal Medicine IV, Friedrich-Alexander-University 91054, Erlangen, Germany [U. K.]

Here we provide proof that the injection of tumor cells engineered to secrete interleukin 2 (IL-2)-IgG chimeric proteins locally induces potent antitumor responses, which are more effective than tumor transfection with IL-2 alone. Murine plasmacytoma cells (J558L) were stably transfected with DNA coding for a human IL-2-IgG1 or a murine IL-2-IgG2b fusion protein and were injected s.c. into syngeneic BALB/c mice. Evaluation of tumor growth and rejection patterns showed that IL-2-IgG secretion by transfected J558L tumor cells induced their rejection in all animals tested, similar to the rejection of J558L cells engineered to secrete IL-2 alone, whereas treatment with parental cells was lethal. However, mice treated with IL-2-IgG-secreting J558L cells (human IL-2-IgG1 and murine IL-2-IgG2b) exhibited a significantly stronger tumor immunity against a later challenge with parental J558L cells than mice treated with IL-2-secreting tumor cells.

¹ This study was supported in part by Grant SFB 506/C5 from the Deutsche Forschungsgemeinschaft (to S. B-P. and T. P.).

² To whom requests for reprints should be addressed, at Institute of Immunology, UKBF, FU Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany. Phone: 49-30-84453639; Fax: 49-30-84454613; E-mail: bulfone@zedat.fu-berlin.de.

Received 3/ 9/98. Accepted 5/15/98.