Vaccines against human HER2 prevent mammary carcinoma in mice transgenic for human HER2.
BACKGROUND
The availability of mice transgenic for the human HER2 gene (huHER2) and prone to the development of HER2-driven mammary carcinogenesis (referred to as FVB-huHER2 mice) prompted us to study active immunopreventive strategies targeting the human HER2 molecule in a tolerant host.


METHODS
FVB-huHER2 mice were vaccinated with either IL-12-adjuvanted human HER2-positive cancer cells or DNA vaccine carrying chimeric human-rat HER2 sequences. Onset and number of mammary tumors were recorded to evaluate vaccine potency. Mice sera were collected and passively transferred to xenograft-bearing mice to assess their antitumor efficacy.


RESULTS
Both cell and DNA vaccines significantly delayed tumor onset, leading to about 65% tumor-free mice at 70 weeks, whereas mock-vaccinated FVB-huHER2 controls developed mammary tumors at a median age of 45 weeks. In the DNA vaccinated group, 65% of mice were still tumor-free at about 90 weeks of age. The number of mammary tumors per mouse was also significantly reduced in vaccinated mice. Vaccines broke the immunological tolerance to the huHER2 transgene, inducing both humoral and cytokine responses. The DNA vaccine mainly induced a high and sustained level of anti-huHER2 antibodies, the cell vaccine also elicited interferon (IFN)-γ production. Sera of DNA-vaccinated mice transferred to xenograft-carrying mice significantly inhibited the growth of human HER2-positive cancer cells.


CONCLUSIONS
Anti-huHER2 antibodies elicited in the tolerant host exert antitumor activity.
Carla
C
De Giovanni
Giordano
G
Nicoletti
Elena
E
Quaglino
Lorena
L
Landuzzi
Arianna
A
Palladini
Marianna Lucia
ML
Ianzano
Massimiliano
M
Dall'Ora
Valentina
V
Grosso
Dario
D
Ranieri
Roberta
R
Laranga
Stefania
S
Croci
Augusto
A
Amici
Manuel L
ML
Penichet
Manuela
M
Iezzi
Federica
F
Cavallo
Patrizia
P
Nanni
Pier-Luigi
PL
Lollini
D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000276:immunology; D061986:MCF-7 Cells; D015674:Mammary Neoplasms, Animal / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008822:Mice, Transgenic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D019444:Vaccines, DNA / Q000276:immunology*
D000906:Antibodies; D019496:Cancer Vaccines; D007371:Interferon-gamma; D018664:Interleukin-12; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA; C508053:ERBB2 protein, human