Murine pneumotropic virus chimeric Her2eu virus-like particles as prophylactic and therapeutic vaccines against Her2eu expressing tumors.

摘要

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 Her2eu and prevented the outgrowth of a human Her2eu expressing tumor in a transplantable tumor model as well as outgrowth of spontaneous rat Her2eu 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 Her2eu. VLPs from MPyV and MPtV carrying human or rat Her2eu were tested in two transplantable tumor models against a human Her2eu positive (D2F2/E2) and a rat Her2eu positive tumor cell line (TUBO). Rat Her2eu-VLPs were also tested in BALB-neuT mice. Her2eu-MPtVLPs were as efficient as prophylactic vaccines against D2F2/E2 and TUBO as those from MPyV. Homologous Her2eu was better than heterologous, i.e. human Her2eu-VLPs were better than rat Her2eu-VLPs against D2F2/E2 and vice versa. Moreover, therapeutic immunization with human Her2eu-VLPs together with CpG given up to 6 days after challenge protected against D2F2/E2. In BALB-neuT mice, rat Her2eu-VLPs were less efficient than human Her2eu-VLPs used in our previous study, implying that protection seen in that study was partly due to the use of human rather than rat Her2eu. In conclusion, Her2eu-MPtVLPs are effective both as prophylactic and therapeutic tumor vaccines. Homologous Her2eu-VLPs are superior to heterologous in transplantable tumor models, while the opposite is true in BALB-neuT mice.