GV1001 is a
telomerase-based
cancer vaccine made of a 16-mer
telomerase reverse transcriptase (TERT)
peptide, and human TERT, the rate-limiting subunit of the
telomerase complex, is an attractive target for
cancer vaccination. The aim of this study was to evaluate the effect of
telomerase peptide vaccination, GV1001 combined with
gemcitabine in treatment of pancreatic ductal adenocardinoma (PDAC). Human PDAC cell lines were used in vitro experiment and also, PDAC xenograft mice model was established using PANC1, AsPC1 and CD133+ AsPC1 (PDAC stem cell). Treatment groups were divided as follows; control,
gemcitabine, GV1001,
gemcitabine and GV1001 combination. The inflammatory
cytokines were measured from the blood, and xenograft
tumor specimens were evaluated. GV1001 treatment alone did not affect the proliferation or the apoptosis of PDAC cells.
Gemcitabine alone and
gemcitabine with GV1001 groups had significantly reduced in
tumor size and showed abundant apoptosis compared to other treatment groups. Surprisingly, xenograft PDAC
tumor specimens of
gemcitabine alone group had been replaced by severe
fibrosis whereas
gemcitabine with GV1001 group had significantly less
fibrosis. Blood levels of
tumor necrosis factor (TNF)-α,
interleukin (IL)-6 and IL-1β increased in
gemcitabine alone group, however, it was decreased in
gemcitabine with GV1001 group. GV1001 combined with
gemcitabine treatment showed significant loss of
fibrosis in
tumor tissue as well as
tumor cell death. Therefore, further investigation of GV1001 effect combined with
gemcitabine treatment may give us useful insights to overcome the hurdle in anti-
cancer drug delivery over massive
fibrosis around PDACs.