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

Int J Oncol. 2014 Sep;45(3):1293-303. doi: 10.3892/ijo.2014.2496. Epub 2014 Jun 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / adverse effects
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / adverse effects
  • Combined Modality Therapy / adverse effects
  • Cytokines / analysis
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage*
  • Granulocyte-Macrophage Colony-Stimulating Factor / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • Peptide Fragments / administration & dosage*
  • Peptide Fragments / adverse effects
  • Telomerase / administration & dosage*
  • Telomerase / adverse effects

Substances

  • Antimetabolites, Antineoplastic
  • Cancer Vaccines
  • Cytokines
  • Peptide Fragments
  • Deoxycytidine
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • gemcitabine
  • GV1001 peptide
  • Telomerase