Safety and efficacy of a genetic vaccine targeting telomerase plus chemotherapy for the therapy of canine B-cell lymphoma

Alessandra Gavazza, George Lubas, Arthur Fridman, Daniela Peruzzi, Joseph A. Impellizeri, Laura Luberto, Emanuele Marra, Giuseppe Roscilli, Gennaro Ciliberto, Luigi Aurisicchio

Research output: Contribution to journalArticlepeer-review

Abstract

Client-owned pet dogs represent exceptional translational models for advancement of cancer research because they reflect the complex heterogeneity observed in human cancer. We have recently shown that a genetic vaccine targeting dog telomerase reverse transcriptase (dTERT) and based on adenovirus DNA electro-gene-transfer (Ad/DNA-EGT) technology can induce strong cell-mediated immune responses against this tumor antigen and increase overall survival of dogs affected by B-cell lymphosarcoma (LSA) in comparison with historical controls when combined with a cyclophosphamide, vincristine, and prednisone (COP) chemotherapy regimen. Here, we have conducted a double-arm clinical trial with an extended number of LSA patients, measured the antigen-specific immune response, and evaluated potential toxic effects of the immunotherapy along with a follow-up of patients survival for 3.5 years. The immune response was measured by enzyme-linked immunospot assay. The expression of dTERT was quantified by quantitative polymerase chain reaction. Changes in hematological parameters, local/systemic toxicity or organic dysfunction and fever were monitored over time during the treatment. dTERT-specific cell-mediated immune responses were induced in almost all treated animals. No adverse effects were observed in any dog patient that underwent treatment. The overall survival time of vaccine/COP-treated dogs was significantly increased over the COP-only cohort (>76.1 vs. 29.3 weeks, respectively, p

Original languageEnglish
Pages (from-to)728-738
Number of pages11
JournalHuman Gene Therapy
Volume24
Issue number8
DOIs
Publication statusPublished - Aug 1 2013

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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