Immunity to breast cancer in mice immunized with X-irradiated breast cancer cells modified to secrete IL-12.
A mouse mammary adenocarcinoma cell line (410.4) originating in a BALB/c mouse, was transduced with a retroviral vector (TGF-mIL-12-Neo) that encoded murine IL-12. After confirmation of IL-12-secretion, the cells were tested for their tumorigenic properties in BALB/c mice. The results indicated that unlike other tumors modified for cytokine secretion, modification of 410.4 cells to secrete IL-12 (410.4-IL-12 cells) failed to eliminate the cells' neoplastic growth properties. Progressively growing tumors of 410.4-IL-12 cells invariably formed in syngeneic BALB/c mice and led, eventually, to the animals' death. However, the cells' immunogenic properties were preserved as indicated by the finding that immunizations with 410.4-IL-12 cells, inactivated before injection by X-irradiation, resulted in potent, long-term immunity toward unmodified 410.4 cells and protected the mice against the malignant proliferation of the breast cancer cells. We conclude that modification of 410.4 cells for IL-12-secretion augmented the response of syngeneic BALB/c mice to weakly immunogenic tumor-associated antigens expressed by the cells. The increase in the cells' immunogenic properties, however, was insufficient to prevent tumor growth in the mice. The results point toward the immunotherapeutic potential of X-irradiated tumor cells modified for the secretion of immune augmenting cytokines.
Carr-Brendel
V
V
Department of Microbiology and Immunology, University of Illinois at Chicago 66012, USA.
Markovic
D
D
Smith
M
M
Taylor-Papadimitriou
J
J
Cohen
E P
EP
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002472:Cell Transformation, Viral; D018450:Disease Progression; D018664:Interleukin-12 / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000235:genetics; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000528:radiation effects* / Q000637:transplantation*; D015164:Vaccines, Inactivated / Q000627:therapeutic use; D014965:X-Rays
D019496:Cancer Vaccines; D015164:Vaccines, Inactivated; D018664:Interleukin-12