A single vaccination with polyomavirus VP1/VP2Her2 virus-like particles prevents outgrowth of HER-2/neu-expressing tumors.
Murine polyomavirus (MPyV) VP1 virus-like particles (VLPs), containing a fusion protein between MPyV VP2 and the extracellular and transmembrane domain of HER-2/neu (Her2), Her2(1-683)PyVLPs, were tested for their ability to vaccinate against Her2-expressing tumors in two different in vivo models. Protection was assessed both against a lethal challenge with a BALB/c mammary carcinoma transfected with human Her2 (D2F2/E2) and against the outgrowth of autochthonous mammary carcinomas in BALB-neuT mice, transgenic for the activated rat Her2 oncogene. A single injection of Her2(1-683)PyVLPs before tumor inoculation induced a complete rejection of D2F2/E2 tumor cells in BALB/c mice. Similarly, a single injection of Her2(1-683)PyVLPs at 6 weeks of age protected BALB-neuT mice with atypical hyperplasia from a later outgrowth of mammary carcinomas, whereas all controls developed palpable tumors in all mammary glands. VLPs containing only VP1 and VP2 did not induce protection. The protection elicited by Her2(1-683)PyVLPs vaccination was most likely due to a cellular immune response because a Her2-specific response was shown in an ELISPOT assay, whereas antibodies against Her2 were not detected in any of the two models. The results show the feasibility of using MPyV-VLPs carrying Her2 fusion proteins as safe and efficient vaccines against Her2-expressing tumors.
Department of Oncology-Pathology, Karolinska Institutet, Cancer Centrum Karolinska, Stockholm, Sweden.
Karin
K
Tegerstedt
Jan Alvar
JA
Lindencrona
Claudia
C
Curcio
Kalle
K
Andreasson
Carl
C
Tullus
Guido
G
Forni
Tina
T
Dalianis
Rolf
R
Kiessling
Torbjörn
T
Ramqvist
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011120:Polyomavirus / Q000235:genetics / Q000276:immunology; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000379:methods
D000914:Antibodies, Viral; D019496:Cancer Vaccines; D036022:Capsid Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; C062481:VP1 protein, polyomavirus; C442543:VP2 protein, Polyomavirus