Protein vaccination with the HER2/neu extracellular domain plus anti-HER2/neu antibody-cytokine fusion proteins induces a protective anti-HER2/neu immune response in mice.
Previously protein vaccines consisting of the extracellular domain of HER2/neu (ECD(HER2)) were shown to elicit an immune response that does not provide protection against transplantable tumors expressing HER2/neu. Here, we showed that when mice were vaccinated with a mixture of human ECD(HER2) and anti-human HER2/neu IL-12, IL-2 or GM-CSF fusion proteins, significant retardation of the growth of a syngeneic carcinoma expressing rat HER2/neu, and long-term survivors were observed. Immune sera inhibited the in vitro growth of SK-BR-3, a human breast cancer overexpressing HER2/neu. Transfer of immune sera into mice challenged with TUBO also led to partial inhibition of tumor growth. Splenocytes from mice vaccinated with ECD(HER2) plus IgG3-(GM-CSF) incubated with ECD(HER2) demonstrated significant proliferation and IFN-gamma secretion. Taken together these results suggest that vaccines including ECD(HER2) and Ab-cytokine fusion proteins may be used to elicit both humoral and cell-mediated responses against HER2/neu.
Dela Cruz
Jay S
JS
Department of Microbiology, The Molecular Biology Institute, University of California, 405 Hilgard Avenue, Los Angeles 90095-1489, USA.
Lau
Suk Ying
SY
Ramirez
Ernesto M
EM
De Giovanni
Carla
C
Forni
Guido
G
Morrison
Sherie L
SL
Penichet
Manuel L
ML
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D005260:Female; D007106:Immune Sera / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014611:Vaccination
D019496:Cancer Vaccines; D016207:Cytokines; D007106:Immune Sera; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins