A vaccine targeting telomerase enhances survival of dogs affected by B-cell lymphoma

Daniela Peruzzi, Alessandra Gavazza, Giuseppe Mesiti, George Lubas, Elisa Scarselli, Antonella Conforti, Claus Bendtsen, Gennaro Ciliberto, Nicola La Monica, Luigi Aurisicchio

Research output: Contribution to journalArticlepeer-review

Abstract

Canine cancers occur with an incidence similar to that of humans and share many features with human malignancies including histological appearance, tumor genetics, biological behavior, and response to conventional therapies. As observed in humans, the telomerase reverse transcriptase (TERT) activity is largely confined to tumor tissues and absent in the majority of normal dog tissues. Therefore, dog TERT (dTERT) can constitute a valid target for translational cancer immunotherapy. We have evaluated the ability of adenovirus serotype 6 (Ad6) and DNA electroporation (DNA-EP) to induce immune responses against dTERT in dogs affected by malignant lymphoma (ML). The vaccine was combined with standard chemotherapy regimen cyclophosphamide, vincristine, prednisone (COP). dTERT-specific immune response was induced in 13 out of 14 treated animals (93%) and remained detectable and long-lasting with the absence of autoimmunity or other side effects. Most interestingly, the survival time of vaccine/Chemo-treated dogs was significantly increased over historic controls of Chemo-treated animals (>97.8 versus 37 weeks, respectively, P = 0.001). Our results show that Ad6/DNA-EP-based cancer vaccine against dTERT overcomes host immune tolerance, should be combined with chemotherapy, induces long-lasting immune responses, and significantly prolongs the survival of ML canine patients. These data support further evaluation of this approach in human clinical trials.

Original languageEnglish
Pages (from-to)1559-1567
Number of pages9
JournalMolecular Therapy
Volume18
Issue number8
DOIs
Publication statusPublished - Aug 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology

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