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Immunizing and Curative Potential of Replicating and Nonreplicating Murine Mammary Adenocarcinoma Cells Engineered with Interleukin (IL)-2, IL-4, IL-6, IL-7, IL-10, Tumor Necrosis Factor , Granulocyte-Macrophage Colony-stimulating Factor, and -Interferon Gene or Admixed with Conventional Adjuvants¹

Department of Clinical and Biological Sciences and Centro Nazionale Ricerche Center for Immunogenetics and Experimental Oncology, University of Turin, Turin, Italy [A. A., M. C., F. C., M. G., T. M., G. F.]; Department of Pathology, Regina Margherita Children's Hospital, Turin, Italy [M. F.]; Institute of Oncology, University of Bologna, Bologna, Italy [P. N., P. L. L.]; Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy [A. G.]; Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy [M. P. C.]; Department of Biotechnology, H. S. Raffaele, Milan, Italy [P. D.]; Institute of Immunology, Freie Universitat Berlin, Berlin, Germany [H. H.]; Max-Delbruck-Centrum fur Molecular Medizin, Berlin, Germany [T. B.]; Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [F. M. R., B. G.]; and Immunobiology Section, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21701-1013 [M. C. B., L. G.]

To evaluate the efficacy of vaccinations with cytokine-gene-transduced tumor cells, BALB/c mice were challenged with 1 x 10⁵ parental cells of a syngeneic adenocarcinoma cell line (TSA-pc). No protection was observed in mice immunized 30 days earlier with 1 x 10⁵ nonreplicating mitomycin-C-treated TSA-pc alone, or with Corynebacterium parvum or Complete Freund Adjuvant (CFA). Ten to 30% of mice immunized with nonreplicating cells engineered to produce interleukin (IL)-2, IL-4, IL-6, IL-7, IL-10, tumor necrosis factor , granulocyte-macrophage colony-stimulating factor, and -interferon gene were protected. Fifty % of mice immunized with replicating TSA-pc admixed with C. parvum and 80–100% of mice immunized with replicating tumor cells transduced with IL-2, IL-4, IL-7, IL-10, or -interferon gene were protected. No cure was afforded by TSA cells admixed with C. parvum or CFA, nor by TSA cells engineered with IL-6, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor gene injected starting 1 day after TSA-pc challenge. Complete tumor regression, however, was obtained in 10–20% of mice treated with TSA cells transduced with IL-2, IL-4, IL-7, or IL-10 and in 30% of those treated with TSA cells transduced with -interferon gene.

¹ This work was supported by grants from the Italian Association for Cancer Research (AIRC), the CNR PF-ACRO, and Deutsche Krebshilfe Milred Scheel Stiftung e.V.

² To whom requests for reprints should be addressed, at CNR-CIOS, Via Santena 19, 10126 Turin, Italy.

Received 8/29/94. Accepted 10/21/94.

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