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applicable to viruses and VP1-VLP which can be dissociated and reas-
sociated chemically. It is potentially useful for the introduction of
encapsulated chemicals into ER.
Exogenous protein encapsulation into VLPs was accomplished by
using the VP1 binding motif of minor capsid proteins. Co-expression
of EGFP fused with the VP1 binding motif of minor capsid proteins
and VP1 in Sf 9 cells produce EGFP containing VLPs. EGFP-VLPs
were analyzed for their ability to be internalized and processed by
mouse cells and to activate mouse and human dendritic cells (DC) in
vitro . 74 EGFP-VLPs entered the mouse epithelial cells, fibroblasts
and human and mouse DC efficiently and were processed by both,
as well as lysosomes and proteasomes. These results provide the basis
for the preparation of mouse polyomavirus capsid-like particles for
transfer of foreign peptides or proteins into cells. The use of foreign
peptide fused with VP2 containing VLPs for vaccination has been
shown. Murine polyomavirus (MPyV), VLPs, containing a fusion
protein between MPyV VP2 and the extracellular and transmem-
brane domain of HER-2/neu (Her2), 75 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, trans-
genic for the activated rat Her2 oncogene. A single injection of Her2
1-683 PyVLPs before tumor inoculation induced a complete rejec-
tion of D2F2/E2 tumor cells in BALB/c mice. Similarly, a single
injection of Her2 1-683 PyVLPs at six weeks of age protected the
BALB/neuT mice with atypical hyperplasia from a later outgrowth
of mammary carcinomas; all the controls developed palpable tumors
in all their 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,
whereas antibodies against Her2 were not detected in both the two
models. The results show it is feasible to use MPyV-VLPs carrying
Her2 fusion proteins as safe and efficient vaccines against Her2-
expressing tumors.
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