EGF receptor-targeted synthetic double-stranded RNA eliminates glioblastoma, breast cancer, and adenocarcinoma tumors in mice

Background Glioblastoma multiforme (GBM) is the most lethal form of
brain cancer. With the available treatments, survival does not
exceed 12-14 mo from the time of diagnosis. We describe a novel
strategy to selectively induce the death of glioblastoma cells and
other cancer cells that over-express the EGF receptor. Using a
non-viral delivery vector that homes to the EGF receptor, we target
synthetic anti-proliferative dsRNA (polyinosine-cytosine poly IC]),
a strong activator of apoptosis, selectively to cancer cells.
Methods and Findings Poly IC was delivered by means of a non-viral
vector: 25kDa polyethylenimine-polyethyleneglycol-EGF
(PEl(25)-PEG-EGF). EGFR-targeted poly IC induced rapid apoptosis in
the target cells in vitro and in vivo. Expression of several
cytokines and ``bystander killing'' of untransfected tumor cells
was detected in vitro and in vivo. Intra-tumoral delivery of the
EGFR-targeted poly IC induced the complete regression of
pre-established intracranial tumors in nude mice, with no obvious
adverse toxic effects on normal brain tissue. A year after
treatment completion the treated mice remain cancer-free and
healthy. Similarly, non-viral delivery of poly IC completely
eliminated pre-established breast cancer and adenocarcinoma
xenografts derived from EGFR over-expressing cancer cell lines,
suggesting that the strategy is applicable to other
EGFR-over-expressing tumors. Conclusion The strategy described has
yielded an effective treatment of EGFR over-expressing GBM in an
animal model. If this strategy is translated successfully to the
clinical setting, it may actually offer help to GBM patients.
Moreover the elimination of two additional EGFR over-expressing
cancers in vivo suggests that in principle this strategy can be
applied to treat other tumors that over-express EGFR.