Abstract
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 adenocarcinoma (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 Surprisingly, xenograft PDAC tumor specimens of gemcitabine alone group had been replaced by severe fibrosis whereas gemcitabine with GV1001 group had significantly less fibrosis.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.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive human cancer and has dismal prognosis with only 6% of patients survive 5 years after diagnosis [14]
GV1001 is a telomerase-based cancer vaccine made of a 16-mer telomerase reverse transcriptase (TERT) peptide, an attractive target for cancer vaccination and the main purpose of this study was to explore the effect of GV1001 when it was combined with gemcitabine in the treatment of pancreatic ductal adenocarcinoma (PDAC)
It was observed that GV1001 did not have direct effects on the proliferation nor the apoptosis of PDAC cells in vitro experiments and we could say that GV1001 did not show direct anti-cancer effects (Figure 1)
Summary
Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive human cancer and has dismal prognosis with only 6% of patients survive 5 years after diagnosis [14]. In spite of the progresses of treatments, the attempts at improving survival of patients with PDAC in the past 15 years, especially in the advanced disease setting, have failed and resulted in no significant improvement [5]. Some chemotherapeutic agents have been used in treatment of PDACs, and gemcitabine became the standard chemotherapeutic agent in pancreatic cancer after randomized trial in 1997 [8]. Pancreatic cancer is highly resistant to chemotherapy including gemcitabine, and the most disappointing circumstance is mainly due to the late diagnosis of PDAC [10, 11]. The best supportive care and maintain the better quality of life are critical since the majority of the patients with PDACs are in advanced stage
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