Telomerase (GV1001) vaccination together with gemcitabine in advanced pancreatic cancer patients

Staff,Caroline; Mozaffari,Fariba; Frödin,Jan-Erik; Mellstedt,Håkan; Liljefors,Maria

doi:10.3892/ijo.2014.2496

Telomerase (GV1001) vaccination together with gemcitabine in advanced pancreatic cancer patients

Authors:
- Caroline Staff
- Fariba Mozaffari
- Jan-Erik Frödin
- Håkan Mellstedt
- Maria Liljefors
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Affiliations: Department of Oncology-Pathology (Radiumhemmet), Karolinska Institutet and Karolinska University Hospital Solna, SE-17176 Stockholm, Sweden, Immune and Gene Therapy Laboratory, Cancer Center Karolinska, Karolinska Institutet and Karolinska University Hospital Solna, SE-17176 Stockholm, Sweden
Published online on: June 11, 2014 https://doi.org/10.3892/ijo.2014.2496
Pages: 1293-1303

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Abstract

Telomerase is expressed in 85-90 % of pancreatic adenocarcinomas and might be a target for active cancer immunotherapy. A study was conducted to investigate safety and immunogenicity in non-resectable pancreatic carcinoma patients using a 16-amino acid telomerase peptide (GV1001) for vaccination in combination with GM-CSF and gemcitabine as first line treatment. Three different vaccine treatment schedules were used; [A (n=6), B (n=6) and C (n=5)]. Groups A/B received GV1001, GM-CSF and gemcitabine concurrently. Group C received initially GV1001 and GM-CSF while gemcitabine was added at disease progression. Group D (n=4) was treated with gemcitabine alone. Adverse events (AE) related to vaccination were mild (grades I-II). Grade III AEs were few and transient. An induced GV 1001‑specific immune response was defined as an increase ≥2 above the baseline value in one of the assays (DTH, proliferation, ELISPOT and cytokine secretion assays, respectively). A telomerase‑specific immune response was noted in 4/6 patients in group A, 4/6 patients in group B and 2/5 patients in group C. An induced ras‑specific immune response (antigenic spreading) was seen in 5 of the 17 patients. The cytokine pattern was that of a Th1-like profile. A treatment induced telomerase or ras response was also noted in group D. All responses were weak and transient. A significant decrease in regulatory T-cells over time was noted in patients in groups A and B (p<0.05). Telomerase vaccination (GV1001) in combination with chemotherapy appeared to be safe but the immune responses were weak and transient. Measures have to be taken to optimize immune responses of GV1001 for it to be considered of clinical interest.

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