Murine pneumotropic virus chimeric Her2/neu virus-like particles as prophylactic and therapeutic vaccines against Her2/neu expressing tumors.
Virus-like particles (VLPs) have increasingly attracted attention as DNA-free and safe antigen carriers in tumor immunotherapy, requiring only minute amounts of antigens. Previously, we have immunized with murine polyomavirus (MPyV) VLPs carrying human Her2/neu and prevented the outgrowth of a human Her2/neu expressing tumor in a transplantable tumor model as well as outgrowth of spontaneous rat Her2/neu carcinomas in BALB-neuT mice. Here, we examine if prophylactic and therapeutic protection could be obtained with murine pneumotropic virus (MPtV) VLPs, and study the cross-reactivity between human and rat Her2/neu. VLPs from MPyV and MPtV carrying human or rat Her2/neu were tested in two transplantable tumor models against a human Her2/neu positive (D2F2/E2) and a rat Her2/neu positive tumor cell line (TUBO). Rat Her2/neu-VLPs were also tested in BALB-neuT mice. Her2/neu-MPtVLPs were as efficient as prophylactic vaccines against D2F2/E2 and TUBO as those from MPyV. Homologous Her2/neu was better than heterologous, i.e. human Her2/neu-VLPs were better than rat Her2/neu-VLPs against D2F2/E2 and vice versa. Moreover, therapeutic immunization with human Her2/neu-VLPs together with CpG given up to 6 days after challenge protected against D2F2/E2. In BALB-neuT mice, rat Her2/neu-VLPs were less efficient than human Her2/neu-VLPs used in our previous study, implying that protection seen in that study was partly due to the use of human rather than rat Her2/neu. In conclusion, Her2/neu-MPtVLPs are effective both as prophylactic and therapeutic tumor vaccines. Homologous Her2/neu-VLPs are superior to heterologous in transplantable tumor models, while the opposite is true in BALB-neuT mice.
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. kalle.andreasson@ki.se
Kalle
K
Andreasson
Karin
K
Tegerstedt
Mathilda
M
Eriksson
Claudia
C
Curcio
Federica
F
Cavallo
Guido
G
Forni
Tina
T
Dalianis
Torbjörn
T
Ramqvist
D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D004247:DNA / Q000378:metabolism; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D011120:Polyomavirus / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*
D019496:Cancer Vaccines; D004247:DNA; D018719:Erb-b2 Receptor Tyrosine Kinases