Long-term immunity elicited by antibody-cytokine fusion proteins protects against sequential challenge with murine mammary and colon malignancies.
We have previously reported that the antibody fusion proteins anti-HER2/neu IgG3 fused to IL-12 [(IL-12)-IgG3] or GM-CSF [IgG3-(GM-CSF)] independently or in combination are effective anti-tumor agents against D2F2/E2 murine mammary cancer cells expressing human HER2/neu in the peritoneum. Importantly, the long-term survivors were immune to the subcutaneous challenge with D2F2/E2 and the parental D2F2 not expressing HER2/neu. We now show that these long-term survivors also exhibit significant protection against subsequent subcutaneous challenge with the murine colon carcinoma CT26-HER2/neu, and later against subcutaneous challenge with the parental CT26. These results suggest that the long-term systemic protection against mammary cancer elicited by treatment with antibody-cytokine fusion proteins can be extended to prevent the growth of a tumor from different origin expressing HER2/neu, and that this protection is not limited to this antigen alone, since it also prevented the growth of the parental tumor cells.
Helguera
Gustavo
G
Division of Surgical Oncology, David Geffen School of Medicine, University of California at Los Angeles, Box 951782, Los Angeles, CA 90095-1782, USA.
Rodríguez
José A
JA
Daniels
Tracy R
TR
Penichet
Manuel L
ML
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D007109:Immunity; D015674:Mammary Neoplasms, Animal / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use*
D000906:Antibodies; D000970:Antineoplastic Agents; D016207:Cytokines; D011993:Recombinant Fusion Proteins